Combination therapy comprising metal channel activator and NMDA receptor antagonist

Abstract

A pharmaceutical composition comprising a metal channel activator and an NMDA receptor antagonist is provided. Also provided is a method of treating depressive disorder comprising administering the pharmaceutical composition. Also provided is a method of treating a neurological or neurodegenerative disorder comprising administering the pharmaceutical composition. Also provided is a method of treating a pain disorder comprising administering the pharmaceutical composition.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This international patent application claims priority to U.S. Provisional Patent Application No. 63 / 402,416, filed on August 30, 2022, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates to combination therapies for the treatment of various medical conditions. In particular, the present invention relates to combinations of metal channel activators and N-methyl-D-aspartate (NMDA) receptor antagonists for the treatment of neurological and neurodegenerative disorders. Background Art

[0004] Metal channel activators (openers) are associated with a wide range of physiological functions including the regulation of electrical properties of excitable cells. + ) and sodium (Na + ) across cell membranes. The primary function of these channels in the brain is to regulate neuronal action potentials. Several neurological disorders may be caused by dysregulation of metal channels.

[0005] Potassium (K + ) channels are present on the plasma membrane of most cell types and are the most diverse class of all ion channels. Voltage-gated potassium (K + Potassium channels of the Kv7 family of ) channels are of particular therapeutic interest because of their importance in neurological conditions such as excitability disorders including amyotrophic lateral sclerosis (ALS). Voltage-gated potassium (K + ) channels have five members in the Kv7 family, including Kv7.1, Kv7.2, Kv7.3, Kv7.4, and Kv7.5.

[0006] It is reported that metal channel activators can be used to treat various neurological and neurodegenerative disorders. So far, only one metal channel activator, Retigabine, has been approved by the FDA. Retigabine is used as an anticonvulsant for the treatment of epilepsy. Other Kv7 channel activators (Vigil FA, Carver CM, Shapiro MS. Pharmacological manipulation of Kv7 channels for the treatment of various morbidities including substance abuse and mood disorders have been proposed (Pharmacological Manipulation of K v 7 Channels as a New Therapeutic Tool for Multiple Brain Disorders). Frontiers in Physiology (Front Physiol.) June 19, 2020; 11: 688. doi: 10.3389 / fphys.2020.00688). However, there is still a need for new therapies utilizing Kv7. One solution is to combine metal channel activators with other therapeutic agents to significantly improve the therapeutic effect.

[0007] NDMA receptor antagonists target the NDMA receptor, a receptor that allows calcium efflux in the presence of glutamate or glycine when neurons are depolarized. NDMA receptor antagonists block calcium efflux and have been used as anesthetics. Recent research has focused on ketamine, which has revealed unexpected antidepressant effects. Lanicemine has been developed as an alternative antidepressant to ketamine with reduced side effects, but has not been successful as a single agent for the treatment of depression in randomized controlled trials.

[0008] This article describes compositions and methods for the combination therapy of Kv7 openers and NMDA receptor antagonists. The combination therapy has a therapeutic ability greater than that of a single Kv7 opener or NMDA receptor antagonist and may be particularly useful for depressive disorders. The pharmaceutical composition combining these agents can also be used to treat pain and neurological or neurodegenerative diseases. These two agents target different molecular targets related to depressive disorders, pain disorders, neurological diseases and neurodegenerative disorders. Specifically, Kv7 channel openers reduce excitability, and NMDA receptor antagonists reduce the outflow of cations such as calcium. It has been found that, as described herein, combining Kv7 openers and NMDA receptor antagonists will produce improved therapeutic results. Summary of the Invention

[0009] The present invention relates to combination therapies comprising a metal channel activator and an NMDA receptor antagonist.

[0010] In one embodiment, a pharmaceutical composition is provided, comprising a metal channel activator and an NMDA receptor antagonist.

[0011] In another embodiment, a method for treating a depressive disorder is provided, comprising administering the pharmaceutical composition.

[0012] In another embodiment, a method of treating a neurological or neurodegenerative disorder comprising administering the pharmaceutical composition is provided.

[0013] In another embodiment, a method of treating a pain disorder is provided, comprising administering the pharmaceutical composition. DETAILED DESCRIPTION

[0014] The following detailed description is provided to assist those skilled in the art in practicing the present invention. Exemplary embodiments will be described in detail below. However, these embodiments are merely exemplary, and the present disclosure is not limited thereto but is defined by the scope of the appended claims. Modifications and variations to the embodiments described herein may be made by those skilled in the art without departing from the spirit or scope of the present disclosure.

[0015] Therefore, the following embodiments are described only by reference to structures and schemes to explain various aspects of this specification. As used herein, the term "and / or" includes any and all combinations of one or more of the associated enumerated items. The term "or" means "and / or". Expressions such as "at least one of...", when preceding a list of elements, modify the entire list of elements rather than the individual elements in the list.

[0016] It should be understood that although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers, and / or sections, these elements, components, regions, layers, and / or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer, or section from another element, component, region, layer, or section. Therefore, without departing from the teachings of the present embodiment, the first element, component, region, layer, or section discussed below may be referred to as a second element, component, region, layer, or section.

[0017] It will be understood that when used in this specification, the terms “comprises” and / or “comprising” or “includes” and / or “including” specify the presence of stated features, regions, integers, steps, operations, elements and / or components, but do not preclude the presence or addition of one or more other features, regions, integers, steps, operations, elements, components and / or groups thereof.

[0018] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this disclosure belongs. The terms used in this specification are only used to describe specific embodiments and are not intended to be limiting. It should be further understood that terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant art and in this disclosure, and unless explicitly defined as such herein, will not be interpreted in an idealized or overly formal sense.

[0019] As used in this application, unless otherwise expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout this application. Where a term is not specifically defined herein, the term is given the art-recognized meaning that one of ordinary skill in the art would apply to the term in the context of its use in describing the present invention.

[0020] The articles "a" and "an" refer to one or more than one (ie, at least one) of the grammatical object of the article unless the context clearly indicates otherwise. For example, "an element" refers to one element or more than one element.

[0021] As used herein, when no specific definition is otherwise provided, the term "substituted" refers to a group substituted with deuterium, halogen (-F, -Cl, -Br, -I), hydroxyl (-OH), amino (-NH2), carboxyl (-CO2H), a substituted or unsubstituted C1-C10 amine group, a nitro (-NO2), a C1-C10 alkyl group, a C3-C10 cycloalkyl group, a C6-C12 aryl group, a C1-C10 alkoxy group, a C1 to C10 trifluoroalkyl group such as trifluoromethyl (-CF3), or a cyano group (-CN), rather than at least one hydrogen of a substituent or compound.

[0022] Additional aspects will be set forth in part in the description which follows and, in part, will be apparent from the description.

[0023] As used herein, "modulator," "modulators," and "modulate" when describing a compound describe a compound that can exert its effect through a variety of mechanisms of action, including but not limited to: binding to the active site of a protein, binding to a region of the protein away from the active site, causing relocation of the protein, inducing degradation of the protein, inducing stabilization of the protein, causing conformational changes in the protein, lowering the activation threshold of the protein, increasing the activation threshold of the protein, changing the post-translational modification of the protein, reducing transcription of a gene, increasing transcription of a gene, reducing translation of an mRNA transcript, increasing translation of an mRNA transcript, disrupting the interaction between two proteins, and stabilizing the interaction between two proteins; wherein the protein can be a target of regulation or an intermediary protein associated with the regulation of the target protein. The modulators of the targets described herein (i.e., Kv7 and NMDA receptors) can each or both be small molecule compounds, proteins, antibody fragments or antibodies, or any other constructs that affect regulation. It should be understood that NMDA receptor antagonists are a type of modulator of NMDA receptors.

[0024] As used herein, "NMDA receptor antagonist" or alternatively "NMDA modulator" means any compound (small molecule, peptide, etc.) that affects the regulation or desired change of the biological activity of the NMDA receptor. In various embodiments, the NMDA receptor antagonist can target a specific portion of the NMDA receptor, such as the GluN1 (alternatively NR1) or GluN2 (alternatively NR2) subunit, or additionally or alternatively the GluN3 subunit. In one embodiment, the NMDA receptor antagonist selectively targets the GluN1 subunit in some cases. In one embodiment, the NMDA receptor antagonist selectively targets one or more GluN2 subtypes GluN2A, GluN2B, GluN2C and / or GluN2D in some cases. In some embodiments, the NMDA receptor antagonist can selectively target one or more GluN3 subtypes GluN3A, GluN3B and / or GluN3C in some cases. In some embodiments, the NMDA receptor antagonist can target an allosteric site. In some embodiments, NMDA receptor antagonists may include partial agonists that exert dual (agonist / antagonist) effects on NMDA receptors. In certain embodiments, NMDA receptor antagonists may include agents with targets other than NMDA receptors that cause NMDA receptor antagonist-like physiological effects.

[0025] As used herein, "neurological disease" refers to a disease or condition that affects the nerves found in the brain and / or elsewhere in the body. Such neurological disorders may include: absent septum pellucidum, acid lipase disease, acute disseminated encephalomyelitis, adrenoleukodystrophy, agenesis of the corpus callosum, agnosia, Aicardi Syndrome, Aicardi-Goutieres Syndrome, Alexander Disease, Alpers' Disease, alternating hemiparesis, Alzheimer's Disease, amyotrophic lateral sclerosis (ALS), anencephaly, Angelman syndrome, antiphospholipid syndrome, aphasia, apraxia, arachnoid cysts, arachnoiditis, arteriovenous malformations, Asperger syndrome, ataxia-telangiectasia, ataxia and cerebellar or spinocerebellar degeneration, atrial fibrillation and stroke, attention deficit hyperactivity disorder, autism spectrum disorder, back pain, Barth syndrome Syndrome), Batten Disease, Behcet's Disease, Bell's Palsy, Benign Essential Blepharospasm, Binswanger's Disease, Brachial Plexus Injury, Brain and Spinal Tumors, Brown-Sequard Syndrome, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), Canavan Disease, Carpal Tunnel Syndrome, Central Cord Syndrome, Central Pain Syndrome Syndrome), central pontine myelinolysis, head disorders, cerebellar degeneration, brain hypoplasia, cerebral aneurysm, cerebral arteriosclerosis, brain atrophy, cerebral cavernous malformation, cerebral hypoxia, cerebral palsy, cerebro-oculofacial-skeletal syndrome (COFS), Charcot-Marie-Tooth disease, Chiari malformation, Chorea, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic pain, Coffin-Lowry syndrome, syringencephaly, coma, complex regional pain syndrome, congenital myasthenia, congenital myopathy, cortical basal degeneration, craniosynostosis, Creutzfeldt-Jakob diseaseDisease, Cushing's Syndrome, Dandy-Walker Syndrome, Deep Brain Stimulation for Movement Disorders, Dementia, Dementia with Lewy Bodies, Dermatomyositis, Developmental Movement Disorders, Diabetic Neuropathy, Dravet Syndrome, Dysautonomia, Dysgraphia, Dyslexia, Dyssynergia Cerebellaris Myoclonica, Dystonia, Empty Sella Syndrome, Encephalitis lethargica, Encephalocele, Encephalopathy, Epilepsy, Erb-Duchenne and Dejerine-Klumpke Palsies, Essential Tremor, Fabry Disease Disease), Fahr's Syndrome, Familial Periodic Paralysis, Farber's Disease, Febrile Seizures, Fibromuscular Dysplasia, Foot Drop, Friedreich Ataxia, Frontotemporal Dementia, Functional Neurological Disorders, Gaucher Disease, Generalized Gangliosidoses, Gerstmann's Syndrome, Gerstmann-Straussler-Scheinker Disease, Giant Axonal Neuropathy, Glossopharyngeal Neuralgia, Guillain-Barré Syndrome, Headache, Migraine Continua, Hemifacial Spasm, Hereditary Neuropathies, Hereditary Spastic Paraplegia, Herpes Zoster Otic, Holmes-Adieu Syndrome Syndrome), holoprosencephaly, Huntington's disease, hydrocephalus, hydrocephalus, hydromyelia, lethargy, hypertonia, hypotonia, inclusion body myositis, incontinentia pigmenti, infantile neuroaxonal dystrophy, infantile Refsum diseaseRefsum Disease), Infantile Spasms, Inflammatory Myopathy, Iniencephaly, Isaacs' Syndrome, Joubert Syndrome, Kearns-Sayre Syndrome, Kennedy's Disease, Kleine-Levin Syndrome, Klippel-Feil Syndrome, Klippel-Trenaunay Syndrome (KTS), Klüver-Bucy Syndrome, Krabbe Disease, Kuru, Lambert-Eaton Myasthenic Syndrome, Landau-Kleffner Syndrome, Learning Disabilities, Leigh's Disease Disease), Lennox-Gastaut Syndrome, Lesch-Nyhan Syndrome, Leukodystrophies, Lipid Storage Diseases, Lipidoid Proteinosis, Lissencephaly, Locked-in Syndrome, Machado-Joseph Disease and Spinocerebellar Ataxia, Macrocephaly, Melkersson-Rosenthal Syndrome, Meningitis and Encephalitis, Menkes Disease, Meralgia Paresthetica, Metachromatic Leukodystrophy, Microcephaly, Migraines, Miller Fisher Syndrome, Mitochondrial Myopathy, Moebius Syndrome Syndrome), Monosomy, Motor Neuron Disease, Moyamoya Disease, Mucolipidemia, Mucopolysaccharidosis, Multi-infarct Dementia, Multifocal Motor Neuropathy, Multiple Sclerosis, Multiple System Atrophy, Multiple System Atrophy with Orthostatic Hypotension, Muscular Dystrophy, Myasthenia Gravis, Myoclonus, Myopathy, Myotonia, Myotonia, Narcolepsy, Neuroacanthocytosis, Neurodegeneration with Brain Iron Accumulation, Neurofibromatosis, Neuroleptic Malignant SyndromeMalignant Syndrome), Neurological Complications of AIDS, Neurological Complications of Lyme Disease, Neurological Consequences of Cytomegalovirus Infection, Neurological Sequelae of Lupus, Neuromyelitis Optica, Neuronal Migration Disorders, Neurosarcoidosis, Neurosyphilis, Neurotoxicity, Niemann-Pick Disease, Normal Pressure Hydrocephalus, Occipital Neuralgia, Ohtahara Syndrome, Olivopontocerebellar Atrophy, Opsoclonus Myoclonus, Orthostatic Hypotension, Paraneoplastic Syndromes, Paresthesias, Parkinson's Disease, Paroxysmal Chorea, Paroxysmal Hemicrania, Parry-Romberg Syndrome, Pelizaeus-Merzbacher Disease, Peripheral Neuropathy, Periventricular Leukomalacia, Pervasive Developmental Disorders, Pinched Nerves Nerve), piriformis syndrome, pituitary tumor, polymyositis, Pompe disease, cerebral perforation, Post-Polio Syndrome, Orthostatic tachycardia syndrome, Primary lateral sclerosis, Progressive multifocal leukoencephalopathy, Progressive supranuclear palsy, Prosopagnosia, Pseudotumor cerebri, Rasmussen's encephalitis, Refsum disease, Repetitive movement disorder, Restless Legs Syndrome, Rett syndrome, Reye's syndrome, Sandhoff disease, Schilder's disease, Schizencephaly, Septo-Optic Dysplasia, Shaken Baby Syndrome, Herpes zoster, Sjögren's syndrome Syndrome, sleep apnea, Sotos Syndrome, spasticity, spina bifida, spinal cord infarction, spinal cord injury, spinal muscular atrophy, stiff-person syndrome, striatonigral degeneration, stroke, Sturge-Weber syndrome, subacute sclerosing panencephalitis, unilateral neuralgic (SUNCT) headache, dysphagia, Sydenham Chorea, syncope, syringomyelia, tabes dorsalis, tardive dyskinesia, Tarlov cysts, Tay-Sachs disease, ethered spinal cord syndrome, thoracic outlet syndrome, thyrotoxic myopathy, Todd's paralysis, Tourette syndrome Syndrome), transient ischemic attack, transmissible spongiform encephalopathy, transverse myelitis, traumatic brain injury, tremor, trigeminal dysmenorrhea, tropical spastic paraparesis, Troyer syndrome, tuberous sclerosis complex, vasculitis syndromes of the central and peripheral nervous systems, Von Hippel-Lindau disease (VHL), Wallenberg's syndrome, Wernicke-Korsakoff syndrome, whiplash, Whipple's disease, Williams syndrome, Wilson disease, and Zellweger syndrome.

[0026] As used herein, the term "metal channel activator" is to be construed to include both metal channel activators and pharmaceutically acceptable salts thereof.

[0027] As used herein, the term "NMDA receptor antagonist" or "NMDA modulator" is to be construed to include both NMDA receptor antagonists and pharmaceutically acceptable salts thereof.

[0028] As used herein, the term "AUC" is the definite integral of the drug concentration in the blood, cerebrospinal fluid, target organ, or any other physiologically relevant site over time following administration. In this context, AUC is used to measure the total exposure of the drug over time. AUC can be assessed over a defined time interval or estimated based on the integral of the drug concentration measured over a time interval extrapolated to infinity.

[0029] As used herein, the term "Cmax" is the maximum concentration of a drug in the blood, cerebrospinal fluid, target organ, or any other physiologically relevant site following administration.

[0030] As used herein, the term "Tmax" is the time it takes for a drug to reach its maximum concentration in the blood, cerebrospinal fluid, target organ, or any other physiologically relevant site following administration.

[0031] As used herein, the term "proteinopathy" refers to a disease characterized by the accumulation or aggregation of a single protein or multiple proteins. Proteinopathies include, but are not limited to, Creutzfeldt-Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and dementia with Lewy bodies.

[0032] Additional aspects will be set forth in part in the description which follows and, in part, will be apparent from the description.

[0033] In the formulas set forth below, substituents and definitions are listed, and the reader should be aware that the substituents and definitions are numbered (e.g., R1, R2, Y, etc.) and are intended to apply to a given formula. The numbering repeated across formulas is intentional and should be read within the context of each specific formula.

[0034] Metal channel activators

[0035] Examples of metal channel activators, including Kv7 channel activators, are disclosed in Formulas 1-171, the "Additional Examples" section, and corresponding referenced applications.

[0036] Formula 1

[0037] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 1. Such compounds are described in U.S. Patent No. 9,481,653, issued on November 1, 2016 and corresponding to U.S. Application No. 14 / 853,815 filed on September 14, 2015; and U.S. Publication No. 20210188782A1, published on June 24, 2021 and corresponding to U.S. Application No. 17 / 127,231 filed on December 18, 2020; the documents are incorporated herein by reference in their entirety. In the event of any conflict in the context of Formula 1, these references are incorporated herein by reference as a reference.

[0038] In one embodiment, the Kv7 channel activator is a compound according to Formula 1:

[0039]

[0040] wherein D is an optionally substituted C 3-6 Carbocyclyl, optionally substituted C 2-5 heterocyclyl, isopropyl or tert-butyl; Bz is an optionally substituted benzimidazole-1,2-diyl; A is C 1-8 alkyl; X is F; and Y is H, F, Cl, Br, I, or a moiety having a molecular weight of 15 to 300 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br.

[0041] In further embodiments, D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or tert-butyl.

[0042] In further embodiments, D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or tert-butyl, wherein each substituent of D and Y (if present) independently has a molecular weight of 15 Da to 200 Da and consists of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br.

[0043] In another embodiment, the Kv7 channel activator is a compound according to Formula 1, wherein D is an optionally substituted C 3-6 Carbocyclyl, optionally substituted C 2-5 heterocyclyl, isopropyl or tert-butyl; Bz is an optionally substituted benzimidazole-1,2-diyl; A is C 1-8alkyl; X is H, F, CF3, optionally substituted phenyl or optionally substituted pyridyl; and Y is H, F, Cl, Br, I or a moiety having a molecular weight of 15 Da to 300 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl or Br.

[0044] In further embodiments, D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or tert-butyl.

[0045] In further embodiments, each substituent of D, X, and Y (if present) independently has a molecular weight of 15 to 200 Da and consists of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br.

[0046] In another embodiment, R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl.

[0047] In further embodiments, X is optionally substituted phenyl.

[0048] In further embodiments, X is CF3.

[0049] In further embodiments, X is optionally substituted pyridinyl.

[0050] In further embodiments, X is H.

[0051] In further embodiments, Y is H.

[0052] In further embodiments, Y is OH.

[0053] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063] Formula 2

[0064] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 2. Such compounds are described in the following: U.S. Patent No. 9,481,653, issued on November 1, 2016, and corresponding to U.S. application No. US14 / 853,815 filed on September 14, 2015; U.S. Patent No. 9,914,708, issued on March 13, 2018, and corresponding to U.S. application No. 15 / 339,590 filed on October 31; U.S. Patent No. 10,385,025, issued on August 20, 2019, and corresponding to U.S. application No. 15 / 879,792 filed on January 25, 2018; U.S. Patent No. 16 / 10,025, issued on February 2, 2021, and corresponding to U.S. application No. 16 / 10,025, filed on July 2, 2019 No. 10,906,877, filed on December 1, 2020, corresponding to U.S. Application No. 16 / 358,642, filed on March 19, 2019; No. 11,261,162, filed on March 1, 2022, corresponding to U.S. Application No. 17 / 077,068, filed on October 22, 2020; and U.S. Publication No. 20210188782A1, published on June 24, 2021, corresponding to U.S. Application No. 17 / 127,231, filed on December 18, 2020; the disclosures are incorporated herein by reference in their entireties. In the event of any conflict in any terminology within the context of Formula 2, these references are incorporated herein by reference.

[0065] In one embodiment, the Kv7 channel activator is a compound according to Formula 2:

[0066]

[0067] wherein D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridyl, isopropyl or tert-butyl; A is C 2-8 alkyl; X is H, F, CF3, optionally substituted phenyl or optionally substituted pyridyl; Y is H, F, Cl, Br, I or a moiety having a molecular weight of 15 to 300 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl or Br; R1 It is F, Cl, Br, CN, OCH3, CHF2, CF3, C 1-4 —CO2-alkyl, C 1-4 Alkyl, -CH2CO2H, -CH2CO2CH2CH3 or -CH2CON(CH3)2 or C 1-5 hydroxyalkyl; and R 2 、R 3 and R 4 It is independently H, F, Cl, Br, I or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl or Br.

[0068] In other embodiments, Y is H, F, CF3, OH, C 1-5 O-alkyl, C 0-6 Alkylamino, optionally substituted tetrahydropyranyl or C 0-6 Fluoroalkylamino.

[0069] In another embodiment, R 1 It is Cl, Br, —OCH3, —CN, —CF3, —CH2OH, —COOCH2CH3, —C(CH3)2OH, —CHOHCH2CH3, —CHOHCH3, —CHF2, —CH(CH3)2, —C(CH2CH3)2OH, —CH2COOCH2CH3, —CH2C(CH3)2OH, —CH2COOH or —CH2CON(CH3)2.

[0070] In another embodiment, R 2 It is H, F, -CH2OH, -CO2Me or -C(CH3)2OH.

[0071] In another embodiment, R 3 It’s H.

[0072] In another embodiment, R 4 It is H, -CH3 or -CF3.

[0073] In another embodiment, R 1 It is Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl.

[0074] In further embodiments, X is optionally substituted phenyl.

[0075] In further embodiments, X is CF3.

[0076] In further embodiments, X is optionally substituted pyridinyl.

[0077] In further embodiments, X is H.

[0078] In further embodiments, Y is H.

[0079] In further embodiments, Y is OH.

[0080] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0081]

[0082]

[0083]

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090] In further embodiments, the Kv7 channel activator is a compound according to Formula 2, wherein D is an optionally substituted cyclobutyl or tert-butyl group; A is C 2-8 Alkyl; X is H, CF3 or optionally substituted phenyl; Y is H or OH; R 1 Is CN or C 1-4 hydroxyalkyl; and R 2 、R 3 and R 4 are independently H or F.

[0091] In another embodiment, R 1 It is CN, -C(CH3)2OH or -CH2C(CH3)2OH.

[0092] In another embodiment, R 2 It's F.

[0093] In another embodiment, R 3 It’s H.

[0094] In another embodiment, R 4 It’s H.

[0095] In another embodiment, R 1 It is CN.

[0096] In another embodiment, R 1 It is C 1-4 Hydroxyalkyl.

[0097] In further embodiments, X is optionally substituted phenyl.

[0098] In further embodiments, X is CF3.

[0099] In further embodiments, X is H.

[0100] In further embodiments, Y is H.

[0101] In further embodiments, Y is OH.

[0102] In another embodiment, the Kv7 channel activator is a compound according to Formula 2, wherein D is cyclobutyl; A is C 1-8 Alkyl; X is CF3; Y is H; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, —CH2OH, —CO2Me or —C(CH3)2OH; R 3 is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br; and R 4 is H, —CH3 or —CF3;

[0103] or

[0104] D is an optionally substituted cyclobutyl; A is C 1-8 Alkyl; X is CF3; Y is H; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, —CH2OH, —CO2Me or —C(CH3)2OH; R 3 is H; and R 4 is H, —CH3 or —CF3;

[0105] or

[0106] D is tert-butyl; A is C 1-8 Alkyl; X is H; Y is H; R1 It is Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, —CH2OH, —CO2Me or —C(CH3)2OH; R 3 is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br; and R 4 is H, —CH3 or —CF3;

[0107] or

[0108] D is tert-butyl; A is C 1-8 Alkyl; X is CF3; Y is H; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, —CH2OH, —CO2Me or —C(CH3)2OH; R 3 is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br; and R 4 is H, —CH3 or —CF3;

[0109] or

[0110] D is cyclobutyl; A is C 1-8 Alkyl; X is H; Y is methyl(2,2,2-trifluoroethyl)amino; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, —CH2OH, —CO2Me or —C(CH3)2OH; R 3 is H; and R 4 is H, —CH3 or —CF3;

[0111] or

[0112] D is cyclobutyl; A is C 1-8 Alkyl; X is CF3; Y is dimethylamino; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C1-4 Hydroxyalkyl; R 2 is H, F, —CH2OH, —CO2Me or —C(CH3)2OH; R 3 is H; and R 4 is H, —CH3 or —CF3;

[0113] or

[0114] D is optionally substituted cyclobutyl, optionally substituted phenyl or optionally substituted C 2-5 alkyl, wherein the optional substituent is selected from -CH3 and F; A is C1 alkyl; X is a substituted cyclobutyl, wherein the substituent is F; Y is H; R 1 is selected from H, C3 hydroxyalkyl, CN, F or Cl; R 2 is selected from H, CN, F, Br or -OCF3; R 3 Selected from H, F or -OCH3; R 4 is H or F; and wherein when X is substituted by 2 fluorine atoms, the fluorine atoms are not geminal; or a pharmaceutically acceptable salt thereof;

[0115] In one embodiment, the Kv7 channel activator is a compound according to Formula 2. 1 、R 2 、R 3 and R 4 It is independently H, F, Cl, Br, I or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl or Br.

[0116] In other embodiments, Y is H, F, CF3, OH, C 1-5 O-alkyl, C 0-6 Alkylamino, optionally substituted tetrahydropyranyl or C 0-6 Fluoroalkylamino.

[0117] In another embodiment, R 1 It is H, Cl, Br, —OCH3, —CN, —CF3, —CH2OH, —COOCH2CH3, —C(CH3)2OH, —CHOHCH2CH3, —CHOHCH3, —CHF2, —CH(CH3)2, —C(CH2CH3)OH, —CH2COOCH2CH3, —CH2C(CH3)2OH, —CH2COOH or —CH2CON(CH3)2.

[0118] In another embodiment, R 2 It is H, F, -CH2OH, -CO2Me or -C(CH3)2OH.

[0119] In another embodiment, R 3 It’s H.

[0120] In another embodiment, R 4 It is H, -CH3 or -CF3.

[0121] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0122]

[0123]

[0124] or a pharmaceutically acceptable salt thereof.

[0125] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0126]

[0127] or a pharmaceutically acceptable salt thereof.

[0128] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0129]

[0130] or a pharmaceutically acceptable salt thereof.

[0131] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0132]

[0133] or a pharmaceutically acceptable salt thereof.

[0134] In further embodiments, the compound is:

[0135]

[0136] or a pharmaceutically acceptable salt thereof.

[0137] In further embodiments, the compound is:

[0138]

[0139] or a pharmaceutically acceptable salt thereof.

[0140] In further embodiments, the compound is:

[0141] or a pharmaceutically acceptable salt thereof.

[0142] In further embodiments, the compound is:

[0143] or a pharmaceutically acceptable salt thereof.

[0144] In further embodiments, the compound is:

[0145] or a pharmaceutically acceptable salt thereof.

[0146] In further embodiments, the compound is:

[0147] or a pharmaceutically acceptable salt thereof.

[0148] In further embodiments, the compound is:

[0149] or a pharmaceutically acceptable salt thereof.

[0150] In further embodiments, the compound is:

[0151]

[0152] or a pharmaceutically acceptable salt thereof.

[0153] In further embodiments, the compound is:

[0154]

[0155] or a pharmaceutically acceptable salt thereof.

[0156] In further embodiments, the compound is:

[0157]

[0158] or a pharmaceutically acceptable salt thereof.

[0159] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0160]

[0161] or a pharmaceutically acceptable salt thereof.

[0162] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0163]

[0164] or a pharmaceutically acceptable salt thereof.

[0165] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0166]

[0167]

[0168] In further embodiments, the compound is:

[0169] or a pharmaceutically acceptable salt thereof.

[0170] In further embodiments, the compound is:

[0171] or a pharmaceutically acceptable salt thereof.

[0172] In further embodiments, the compound is:

[0173]

[0174] or a pharmaceutically acceptable salt thereof.

[0175] In further embodiments, the compound is:

[0176] or a pharmaceutically acceptable salt thereof.

[0177] In further embodiments, the compound is:

[0178] or a pharmaceutically acceptable salt thereof.

[0179] In further embodiments, the compound is:

[0180]

[0181] or a pharmaceutically acceptable salt thereof.

[0182] In further embodiments, the compound is:

[0183] or a pharmaceutically acceptable salt thereof.

[0184] In further embodiments, the compound is:

[0185]

[0186] or a pharmaceutically acceptable salt thereof.

[0187] In further embodiments, the compound is:

[0188] or a pharmaceutically acceptable salt thereof.

[0189] In further embodiments, the compound is:

[0190]

[0191] or a pharmaceutically acceptable salt thereof.

[0192] In further embodiments, the compound is:

[0193]

[0194] or a pharmaceutically acceptable salt thereof.

[0195] In further embodiments, the compound is:

[0196]

[0197] or a pharmaceutically acceptable salt thereof.

[0198] In the embodiment of Formula 2, D is an optionally substituted cyclobutyl or tert-butyl group; A is C 2-8 Alkyl, X is H, CF3 or optionally substituted phenyl, Y is H or OH, R 1 Is CN or C 1-4 hydroxyalkyl; and R 2 、R 3 and R 4 are independently H or F. In another embodiment, R 1 is CN, -C(CH3)2OH or -CH2C(CH3)2OH. In another embodiment, R 2 is F. In another embodiment, R 3 is H. In another embodiment, R 4 is H. In another embodiment, R 1 is CN. In another embodiment, R 1 It is C 1-4 In another embodiment, X is optionally substituted phenyl. In another embodiment, X is CF3. In another embodiment, X is H. In another embodiment, Y is H. In another embodiment, Y is OH.

[0199] In the embodiment of Formula 2, D is cyclobutyl; A is C 1-8 Alkyl, X is CF3, Y is H, R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2is H, F, -CH2OH, -CO2Me or -C(CH3)2OH; R 3 is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or B; and R 4 It is H, -CH3 or -CF3.

[0200] In the embodiment of Formula 2, D is an optionally substituted cyclobutyl, A is C 1-8 Alkyl, X is CH3, Y is H, R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, -CH2OH, -CO2Me or -C(CH3)2OH; R 3 is H; and R 4 It is H, -CH3 or -CF3.

[0201] In the embodiment of Formula 2, D is tert-butyl; A is C 1-8 Alkyl; X is H; Y is H; R 1 It is Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, -CH2OH, -CO2Me or -C(CH3)2OH; R 3 is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br; and R 4 It is H, -CH3 or -CF3.

[0202] In the embodiment of Formula 2, D is tert-butyl; A is C 1-8 Alkyl; X is CF3; Y is H; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, -CH2OH, -CO2Me or -C(CH3)2OH; R 3 is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 to 200 Da and consisting of 2 to 5 chemical elements, wherein the chemical elements are independently C, H, O, N, S, F, Cl, or Br; and R4 It is H, CH3 or CF3.

[0203] In the embodiment of Formula 2, D is cyclobutyl; A is C 1-8 Alkyl; X is H; Y is methyl(2,2,2-trifluoroethyl)amino; R 1 It is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 2 is H, F, -CH2OH, -CO2Me or -CH(CH3)2OH; R 3 is H; and R 4 It is H, -CH3 or -CF3.

[0204] In the embodiment of Formula 2, D is optionally substituted cyclobutyl, optionally substituted phenyl or optionally substituted C 2-5 alkyl, wherein the optional substituent is selected from -CH3 and F; A is C1 alkyl, X is a substituted cyclobutyl, wherein the substituent is F; Y is H; R 1 is selected from H, C3 hydroxyalkyl, CN, F or Cl; R 2 is selected from H, CN, F, Br or -OCF3; R 3 is selected from H, F or -OCH3; R 4 is H or F; and wherein when X is substituted by 2 fluorine atoms, the fluorine atoms are not geminal; or a pharmaceutically acceptable salt thereof.

[0205] Formula 3

[0206] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 3. Such compounds are described in U.S. Patent No. 8,293,911, issued on October 23, 2012, corresponding to U.S. Application No. 11 / 894,877 filed on August 22, 2007; the document is incorporated herein by reference in its entirety. In the event of any conflict in the context of Formula 3, this reference is incorporated herein by reference.

[0207] In one embodiment, the Kv7 channel activator is a compound according to Formula 3:

[0208]

[0209] wherein R1 and R2 vary independently and are selected from the group consisting of: H, CN, halogen, CH2CN, OH, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl; NH—C1-C6 alkyl; N(C1-C6 alkyl)-C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH2, C(═O)NH—C1-C6 alkyl, SO2NH2, NHSO2—C1-C6 alkyl; C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2) m C3-C6 cycloalkyl 、 C3-C6 cycloalkenyl, (CH2) m C3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CH2) m Thiphenyl, (CH2) m Imidazole, (CH2) m Pyrazolyl, (CH2) m Oxazolyl, (CH2) m Isoxazolyl, (CH2) m Thiazolyl, (CH2) m Isothiazolyl, (CH2) m Phenyl, (CH2) m Pyrrolyl, (CH2) m Pyridyl and (CH2) m pyrimidinyl, wherein m=0, 1 or 2; Ar is a 5- to 10-membered monocyclic or bicyclic aromatic group, optionally containing 1-4 ring heteroatoms independently selected from N, O and S; or R1 and R2 together with the ring carbon atoms to which they are attached form a 5- or 6-membered fused ring; wherein the fused ring may be saturated, unsaturated or aromatic, and the fused ring optionally contains one or two heteroatoms independently selected from the group consisting of O, N and S; R' is selected from the group consisting of H, halogen, phenyl, 2-(N,N-dimethylamino)ethyl, CF3, OC1-C3 alkyl and C1-C3 alkyl; R3 and R4 vary independently and are selected from the group consisting of H, CN, halogen, CF3, OCF3, OC1-C3 alkyl and C1-C3 alkyl; X is O or S; Y is O or S; q=1 or zero; and R5 is selected from the group consisting of C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3-C6 cycloalkyl, CH2(CHR6) wC3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar and (CHR6) w CH2Ar, wherein w = zero, 1, 2 or 3; Ar is a 5- to 10-membered monocyclic or bicyclic aromatic group, optionally containing 1-4 ring heteroatoms independently selected from the group consisting of N, O and S; and R6 is selected from the group consisting of H or C1-C3 alkyl; wherein all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms independently selected from N, O and S; wherein all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl and heteroaryl groups in R1, R2, R', R3, R4, R5, R6 and Ar are optionally substituted with one or two substituents independently selected from the group consisting of: C1-C3 alkyl, halogen, OH, OEt, OMe, CN, CH2F, OCF3 and CF3; and wherein, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with carbonyl.

[0210] In other embodiments, R1 and R2 vary independently and are selected from the group consisting of H, halogen, CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SCH3, C3-C6 cycloalkyl, (CH2) m C3-C6 cycloalkyl, phenyl, pyridyl, pyrrolyl, thienyl, (CH2) m Phenyl, (CH2) m Pyrrolyl and (CH2) m wherein the cycloalkyl group optionally contains one or two heteroatoms independently selected from the group consisting of O, N, and S; wherein the alkyl, cycloalkyl, phenyl, pyrrolyl, and pyridyl group are optionally substituted with one or two groups independently selected from halogen, methyl, ethyl, or trifluoromethyl; and wherein m is zero, 1, or 2; R' is selected from the group consisting of H, halogen, phenyl, 2-(N,N-dimethylamino)ethyl, CF3, OC1-C3 alkyl, and C1-C3 alkyl; R3 and R4 vary independently and are selected from the group consisting of H, halogen, CF3, OCF3, OC1-C3 alkyl, and C1-C3 alkyl; X is O or S; Y is O or S; q=1 or 0; R5 is selected from the group consisting of C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6)w CH2C3-C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar and (CHR7) w CH2Ar, wherein w=0-3; Ar is selected from the group consisting of phenyl, pyrimidinyl or pyridinyl and a 5-membered heteroaromatic ring; wherein the heteroaromatic ring contains 1 or 2 ring heteroatoms independently selected from the group consisting of N, O and S; and R6 is selected from the group consisting of H and methyl; wherein all cycloalkyl and cycloalkenyl groups in R5 optionally contain one or two ring heteroatoms independently selected from the group consisting of N, O and S; and wherein all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl and heteroaryl groups in R1, R2, R3, R4, R5, R6 and Ar are optionally substituted with one or two substituents independently selected from the group consisting of C1-C3 alkyl, halogen, OEt, OMe and trifluoromethyl.

[0211] In other embodiments, R1 and R2 vary independently and are selected from the group consisting of H, halogen, CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SCH3, (CH2) m Cycloalkyl, (CH2) m Cyclobutyl, (CH2) m Cyclopentyl, (CH2) m Cyclohexyl, (CH2) m Oxazolyl, (CH2) m Isoxazolyl, (CH2) m Thiazolyl, (CH2) m Isothiazolyl, (CH2) m Phenyl, (CH2) m Pyrrolyl, (CH2) m Pyridyl and (CH2) mpyrimidinyl; wherein the cyclopentyl and the cyclohexyl optionally contain one or two ring heteroatoms independently selected from the group consisting of O, N and S; wherein the alkyl, cycloalkyl, phenyl, pyrrolyl and pyridyl are optionally substituted with one or two groups independently selected from the group consisting of: halogen, CH3, ethyl and CF3; and m is zero, 1 or 2; R' is selected from the group consisting of: H, halogen, CF3 and C1-C3 alkyl; R3 and R4 vary independently and are selected from the group consisting of: H, halogen, CF3, OCF3, OC1-C3 alkyl and C1-C3 alkyl; X is O or S; Y is O; q=1 or 0; R5 is selected from the group consisting of: C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3-C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar and (CHR6) w CH2Ar, wherein w=0-3, Ar is selected from the group consisting of phenyl, pyridyl and a 5-membered heteroaromatic ring, wherein the heteroaromatic ring contains 1 or 2 ring heteroatoms independently selected from the group consisting of N, O and S; R6 is H or methyl; wherein all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms independently selected from the group consisting of N, O and S; and wherein all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl and heteroaryl groups in R1, R2, R3, R4, R5, R6 and Ar are optionally substituted with one or two substituents independently selected from the group consisting of: C1-C3 alkyl, halogen, OMe, OEt and CF3.

[0212] In further embodiments, R1 and R2 vary independently and are selected from the group consisting of: H, halogen, CF3, OC1-C3 alkyl, C1-C6 alkyl, C(═O)OC1-C3 alkyl, OC(═O)C1-C3 alkyl, and C(═O)C1-C3 alkyl; R' is selected from the group consisting of: H, F, CH3, and ethyl; R3 and R4 vary independently and are selected from the group consisting of: H, F, Cl, CF3, OCF3, OC1-C3 alkyl, and C1-C3 alkyl; and R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6)w CH2C3-C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl or (CHR6) w Ar, CH2(CHR6) w Ar or (CHR6) w CH2Ar.

[0213] In further embodiments, R2 is H or F; R' is H; R3 is selected from the group consisting of: H, CH3, OCH3, CF3, OCF3, and Cl; R4 is selected from the group consisting of: CH3, OCH3, CF3, OCF3, and Cl; and R5 is C3-C6 alkyl or (CH2) w C3-C6 cycloalkyl group.

[0214] In further embodiments, R1 is halogen or CF3; R2 is H or F; R' is H; R3 and R4 vary independently and are selected from the group consisting of: H, CH3, OCH3, CF3, OCF3 or Cl; and R5 is selected from the group consisting of: C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3-C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar and (CHR6) w CH2Ar.

[0215] In further embodiments, R1 is halogen or CF3; R2 is H or F; R' is H; R3 and R4 vary independently and are selected from the group consisting of: H, CH3, OCH3, CF3, OCF3 or Cl; and R5 is selected from the group consisting of: C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3-C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar and (CHR6) w CH2Ar.

[0216] Formula 4

[0217] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 4. Such compounds are described in U.S. Patent No. 8,293,911, issued on October 23, 2012, and corresponding to U.S. Application No. 11 / 894,877; the document is incorporated herein by reference in its entirety. In the event of any conflict in the context of Formula 4, this reference is incorporated herein by reference.

[0218] In one embodiment, the Kv7 channel activator is a compound according to Formula 4:

[0219]

[0220] wherein R1 is selected from the group consisting of: H, halogen, CN, CH2CN, CF3, C1-C6 alkyl, OCH3, (C═O)OCH3, O(C═O)CH3, OCF3, (CH2) m C3-C6 cycloalkyl, phenyl and pyridyl; R2 is selected from the group consisting of: H, F, OCH3, CH3 and CF3; R3 and R4 are independently varied and are selected from the group consisting of: H, F, Cl, CF3, OCF3, OC1-C3 alkyl or C1-C3 alkyl; and R5 is selected from the group consisting of: C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3-C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar and (CHR6) wCH2Ar; wherein w=0-3; Ar is phenyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, thienyl or pyridyl; and R6 is C1-C3 alkyl; wherein all alkyl, cycloalkyl, aryl and heteroaryl groups in R1, R2, R3, R4, R5, R6 and Ar are optionally substituted with one or two substituents independently selected from the group consisting of C1-C3 alkyl, halogen, OCH3, OCH2CH3, CN and CF3.

[0221] In other embodiments, R1 is selected from the group consisting of H, F, Cl, Br, CF3, C1-C6 alkyl, OCH3, CHOCH3, CH2CH2OCH3, CHOCH2CH3, and OCH2CH3; R' is selected from the group consisting of H, CH3, CH2CH3, or halogen; R3 and R4 vary independently and are selected from the group consisting of H, F, Cl, CF3, OCF3, OCH3, and CH3; and R5 is selected from the group consisting of C1-C6 alkyl, CH2C3-C6 cycloalkyl, CH2CH2C3-C6 cycloalkyl, CH═CH—C3-C6 cycloalkyl, CH═CH—C5-C6 cycloalkenyl, CH2C5-C6 cycloalkenyl, CH2CH2C5-C6 cycloalkenyl, C2-C6 alkenyl, and (CH2) w Ar; wherein w = 1 or 2; Ar is selected from the group consisting of phenyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, furyl, thienyl, pyrrolyl and pyridyl; wherein all alkyl, cycloalkyl, aryl and heteroaryl groups in R1, R2, R3, R4, R5, R6 and Ar are optionally substituted with one or two substituents independently selected from the group consisting of CH3, halogen, OCH3, OCH2CH3, CN and CF3.

[0222] In other embodiments, R1 is selected from the group consisting of H, F, Cl, Br, CF3, C1-C6 alkyl, OCH3, CHOCH3, CH2CH2OCH3, CHOCH2CH3, and OCH2CH3; R' is selected from the group consisting of H, CH3, CH2CH3, or halogen; R3 and R4 vary independently and are selected from the group consisting of H, F, Cl, CF3, OCF3, OCH3, and CH3; and R5 is selected from the group consisting of C1-C6 alkyl, CH2C3-C6 cycloalkyl, CH2CH2C3-C6 cycloalkyl, CH═CH—C3-C6 cycloalkyl, CH═CH—C5-C6 cycloalkenyl, CH2C5-C6 cycloalkenyl, CH2CH2C5-C6 cycloalkenyl, C2-C6 alkenyl, and (CH2) wAr; wherein w = 1 or 2; Ar is selected from the group consisting of phenyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, furyl, thienyl, pyrrolyl and pyridyl; wherein all alkyl, cycloalkyl, aryl and heteroaryl groups in R1, R2, R3, R4, R5, R6 and Ar are optionally substituted with one or two substituents independently selected from the group consisting of CH3, halogen, OCH3, OCH2CH3, CN and CF3. wherein R1 is selected from the group consisting of: F, CF3, Cl, CH3, CH2CH3, SCH3, OCH3, CHOCH3, CHOCH2CH3, OCF3, phenyl, thienyl, and H; R2 is selected from the group consisting of: H, F, Cl, and OCH3; R' is selected from the group consisting of: H, F, CH2CH3, and CH3; R3 and R4 vary independently and are selected from the group consisting of: H, Cl, CH3, CF3, OCH3, and OCF3; and R5 is selected from the group consisting of: C4-C6 alkyl, (CH2) w Ar and (CH2) w C5-C6 cycloalkyl; wherein w is 1, 2 or 3.

[0223] In other embodiments, R1 is selected from the group consisting of: F, CF3, Cl, CH3, OCH3, CHOCH3, and H; R2 is selected from the group consisting of: H, F, CH3, and Cl; R' is H; R3 is selected from the group consisting of: H, Cl, CH3, CF3, OCH3, and OCF3; R4 is selected from the group consisting of Cl, OCH3, and CH3; and R5 is C4-C6 alkyl or 2-cyclopentylethyl.

[0224] In other embodiments, R3 and R4 are both CH3 or both OCH3; and R5 is C5-C6 alkyl.

[0225] In other embodiments, R' and R2 are H; R3 and R4 are both methyl; and R5 is C5-C6 alkyl or (CH2) w C5-C6 cycloalkyl; wherein w is 1, 2 or 3.

[0226] In other embodiments, the compound is selected from the group consisting of: N-(2-chloro-4-(3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethyl)phenyl)-3,3-dimethylbutanamide; N-(4-(3,4-dihydroisoquinolin-2(1H)-yl)-2,6-dimethylphenyl)-3,3-dimethylbutanamide; N-(2-chloro-4-(3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethyl)phenyl)-3-cyclopentylpropionamide; N-(2-chloro-4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethylphenyl)-3,3-dimethylbutanamide; N-[2-chloro-4-(3,4-dihydroisoquinolin-2(1H)-yl)-2,6-dimethylphenyl)-3,3-dimethylbutanamide. N-[2-Chloro-4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethylphenyl]-3-cyclopentylpropionamide; N-[2,6-dimethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide; N-[2-Chloro-6-trifluoromethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide; N-[2-Chloro-4-(6-chloro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethylphenyl]- 3,3-dimethylbutyramide; N-[4-(6-chloro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutyramide; N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutyramide; N-[2-chloro-4-(7-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethyl-phenyl]-3,3-dimethylbutyramide; N-[4-(7-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutyramide; N-[2-chloro-4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutyramide -1H-isoquinolin-2-yl)-6-methylphenyl]-3,3-dimethylbutanamide; N-[2-chloro-4-(7-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6-methylphenyl]-3,3-dimethylbutanamide; N-[2-chloro-6-methyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide; N-[2-chloro-4-(6-chloro-3,4-dihydro-1H-isoquinolin-2-yl)-6-methyl-phenyl]-3,3-dimethylbutanamide; N-[2-chloro-4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide;N-[4-(6-Fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2-methyl-phenyl]-3,3-dimethylbutanamide; N-[4-(6-Fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2-trifluoromethylphenyl]-3,3-dimethylbutanamide; N-[2-Chloro-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide; N-[4-(7-Fluoro-3,4-dihydro-1H -isoquinolin-2-yl)-2-trifluoromethyl-phenyl]-3,3-dimethylbutanamide; 3,3-dimethyl-N-[2-trifluoromethyl-4-(7-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]butanamide; N-[4-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutanamide; N-[4-(3,4-dihydro-1H-isoquinolin-2-yl)-2-methoxy -6-methyl-phenyl]-3,3-dimethylbutanamide; N-[2-chloro-4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethoxy-phenyl]-3,3-dimethylbutanamide; N-[4-(3,4-dihydro-M-isoquinolin-2-yl)-2,6-dimethoxy-phenyl]-3,3-dimethylbutanamide; N-[2,6-dimethyl-4-(7-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide Methylbutanamide; N-[2,6-dimethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethyl-thiobutanamide; [2,6-dimethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-carbamic acid ethyl ester; and N-[2,6-dimethyl-4-(7-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide.

[0227] Formula 5

[0228] In another embodiment, the Kv7 channel activator can be selected from one of the following compounds. Such compounds are described in the following: U.S. Patent No. 8,993,593, issued on March 31, 2015 and corresponding to U.S. Application No. 12 / 698,070 filed on February 1, 2010; U.S. Publication No. US20220265634A1, published on August 25, 2022 and corresponding to U.S. Application No. 17 / 668,340 filed on February 9, 2022; the document is incorporated herein by reference in its entirety. In the event of any conflict of terms in the context of Formula 5, these references are incorporated herein by reference as a control.

[0229] In one embodiment, the Kv7 channel activator is a compound according to Formula 5:

[0230]

[0231] Optionally wherein the compound is substituted at any position.

[0232] Formula 6

[0233] In another embodiment, the Kv7 channel activator can be the following compound (ezogabine, also known as retigabine) or a pharmaceutically acceptable salt thereof.

[0234] In the event of any conflict in the context of Formula 6, these references are incorporated herein by reference.

[0235]

[0236] Alternatively, optionally, wherein the compound is substituted at any position.

[0237] Formula 7

[0238] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 7. Such compounds are described in the following: U.S. Patent No. 10,526,328, issued on January 7, 2020, corresponding to U.S. Application No. 16 / 124,853, filed on September 7, 2018; U.S. Patent No. 10,106,536, issued on October 23, 2018, corresponding to U.S. Application No. 15 / 591,844, filed on May 10, 2017; No. 9,650,376, issued May 16, 2014, and corresponding to U.S. application Ser. No. 14 / 776,271, filed March 17, 2014; and U.S. Publication No. US20220060208A1, published February 24, 2022, and corresponding to U.S. application Ser. No. 17 / 277,145, filed January 14, 2019; the disclosures of which are incorporated herein by reference in their entireties. In the event of any conflict in any terminology within the context of Formula 7, these references are hereby incorporated by reference herein for all purposes.

[0239] In one embodiment, the Kv7 channel activator is a compound according to Formula 7:

[0240]

[0241] Wherein, L is CH2; R1 is an optionally substituted cyclic C3H5, wherein R 1 The optional substituent is CF3; R 2 is optionally substituted cyclobutyl; R 3 is an optionally substituted C3 alkyl group, wherein R 3 The optional substituent is OH; R 4 is H; and R 5 It is H;

[0242] or

[0243] Wherein, L is CH2; R 1 is an optionally substituted C2 alkyl group, wherein R 1 The optional substituents are independently CF3 or CH3; R 2 is optionally substituted cyclobutyl; R 3 is an optionally substituted C3 alkyl group, wherein R 3 The optional substituent is OH; R 4 is H; and R 5 It is H;

[0244] or

[0245] wherein L is CH2, CF2, CHCH3, CH2CH2, C3H6, CH2O, C2H4O or C3H6O, wherein O of CH2O, C2H4O or C3H6O is the same as R 1 bonding; where R 1 is an optionally substituted C 1-2 Alkyl, optionally substituted C 5-10 Cycloalkyl, optionally substituted C 1-12 -O-alkyl, optionally substituted C 6-10 Aryl, optionally substituted C 6-10 -O-aryl or optionally substituted C 2-9 Heterocyclic group, wherein R 1 The optional substituents are independently R A 、F、Cl、CN、OR A 、CF3、NR A R B 、COR A 、CO2R A , OCOR A NR A COR B 、CONR A R B , where R A and R B are independently H or C 1-12 Alkyl; wherein R 2 is an optionally substituted C 2-4acyclic alkyl, optionally substituted cyclobutyl, optionally substituted C 6-10 Aryl or optionally substituted C 2-9 Heterocyclic group, wherein R 2 The optional substituents are independently F, Cl, Br, I, CN, C 1-6 Alkyl, C 1-6 —O-alkyl, C 1-6 Alkylamine, C 1-6 aminoalkyl, C 1-6 Aminoacyl, C 1-6 Alkylthio or C 1-6 Alkylsulfonyl; wherein R 3 、R 4 and R 5 are independently H, F, Cl, Br, I, CN, optionally substituted C 1-12 Alkyl, optionally substituted C 1-12 -O-alkyl, optionally substituted C 2-9 Heterocyclyl, optionally substituted C 6-10 Aryl, optionally substituted C 2-9 -O-heterocyclyl, optionally substituted C 6-10 O-aryl, optionally substituted C 1-12 Acylamino, optionally substituted C 1-12 aminoacyl or optionally substituted C 1-12 aminoalkyl, where R 3 、R 4 or R 5 The optional substituents are independently F, Cl, Br, I, CN, C 1-6 Alkyl, C 1-6 —O-alkyl, C 1-6 Alkylamine, C 1-6 aminoalkyl, C 1-6 Aminoacyl, C 1-6 Acylamino, C 1-6 Alkylthio or C 1-6 Alkylsulfonyl.

[0246] In another embodiment, R 2 is optionally substituted C4H9, optionally substituted cyclobutyl, optionally substituted C 6-10 Aryl or optionally substituted C 2-9 Heterocyclic group.

[0247] In another embodiment, R 2 is optionally substituted C4H9 or optionally substituted cyclobutyl.

[0248] In another embodiment, R 2 is optionally substituted phenyl or optionally substituted C 2-9 Heterocyclic group.

[0249] In another embodiment, R 1 is optionally substituted phenyl.

[0250] In another embodiment, R 1 is optionally substituted phenyl.

[0251] In another embodiment, R 1 is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0252] In another embodiment, R 1 It is C 2-4 —O-alkyl.

[0253] In another embodiment, R 1 is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl.

[0254] In another embodiment, R 1 Selected from the group consisting of:

[0255]

[0256] In another embodiment, R 2 Selected from the group consisting of:

[0257] In another embodiment, R 3 is CF3, Cl, CN, OCH3 or H. In another embodiment, R 1 Selected from the group consisting of:

[0258]

[0259] In another embodiment, R 4 It is CH3, CF3, Cl or H.

[0260] In another embodiment, R 2 Selected from the group consisting of:

[0261]

[0262] In further embodiments, the Kv7 channel activator is selected from the group consisting of:

[0263]

[0264]

[0265]

[0266]

[0267]

[0268] In further embodiments, the Kv7 channel activator is selected from the group consisting of:

[0269]

[0270]

[0271]

[0272]

[0273]

[0274]

[0275]

[0276]

[0277]

[0278]

[0279]

[0280] Formula 8

[0281] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 8. Such compounds are described in U.S. Patent No. 9,650,376, published on February 4, 2014, corresponding to U.S. Application No. 14 / 776,271 filed on March 17, 2014; the entirety of which is incorporated herein by reference. In the event of any conflict in the context of Formula 8, this reference is incorporated herein by reference.

[0282] In one embodiment, the Kv7 channel activator is a compound according to Formula 8:

[0283]

[0284] Wherein, L is CH2, CF2, CHCH3, CH2CH2, C3H6, CH2O, C2H4O or C3H6O, wherein O of CH2O, C2H4O or C3H6O is the same as R 1 bonding; where R 1 is an optionally substituted C 1-2Alkyl, optionally substituted C 5-10 Cycloalkyl, optionally substituted C 1-12 -O-alkyl, optionally substituted C 6-10 Aryl, optionally substituted C 6-10 -O-aryl or optionally substituted C 2-9 Heterocyclic group, wherein R 1 The optional substituents are independently R A 、F、Cl、CN、OR A 、CF3、NR A R B 、COR A 、CO2R A , OCOR A NR A COR B 、CONR A R B , where R A and R B are independently H or C 1-12 Alkyl; wherein R 2 is an optionally substituted C 2-4 acyclic alkyl, optionally substituted cyclobutyl, optionally substituted C 6-10 Aryl or optionally substituted C 2-9 Heterocyclic group, wherein R 2 The optional substituents are independently F, Cl, Br, I, CN, C 1-6 Alkyl, C 1-6 —O-alkyl, C 1-6 Alkylamine, C 1-6 aminoalkyl, C 1-6 Aminoacyl, C 1-6 Alkylthio or C 1-6 Alkylsulfonyl; wherein R 3 、R 4 and R 5 are independently H, F, Cl, Br, I, CN, optionally substituted C 1-12 Alkyl, optionally substituted C 1-12 -O-alkyl, optionally substituted C 2-9 Heterocyclyl, optionally substituted C 6-10 Aryl, optionally substituted C 2-9 -O-heterocyclyl, optionally substituted C 6-10 O-aryl, optionally substituted C 1-12 Acylamino, optionally substituted C 1-12 aminoacyl or optionally substituted C 1-12 aminoalkyl, where R 3 、R 4 or R 5The optional substituents are independently F, Cl, Br, I, CN, C 1-6 Alkyl, C 1-6 —O-alkyl, C 1-6 Alkylamine, C 1-6 aminoalkyl, C 1-6 Aminoacyl, C 1-6 Acylamino, C 1-6 Alkylthio or C 1-6 Alkylsulfonyl.

[0285] In another embodiment, R 2 is optionally substituted C4H9, optionally substituted cyclobutyl, optionally substituted C 6-10 Aryl or optionally substituted C 2-9 Heterocyclic group.

[0286] In another embodiment, R 2 is optionally substituted C4H9 or optionally substituted cyclobutyl.

[0287] In another embodiment, R 2 is optionally substituted phenyl or optionally substituted C 2-9 Heterocyclic group.

[0288] In another embodiment, R 1 is optionally substituted phenyl.

[0289] In another embodiment, R 1 is optionally substituted phenyl.

[0290] In another embodiment, R 1 is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0291] In another embodiment, R 1 It is C 2-4 —O-alkyl.

[0292] In another embodiment, R 1 is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl. In further embodiments, R 1 Selected from the group consisting of:

[0293]

[0294] In another embodiment, R 2 Selected from the group consisting of:

[0295]

[0296] In another embodiment, R 3is CF3, Cl, CN, OCH3 or H. In another embodiment, R 1 Selected from the group consisting of:

[0297]

[0298] In another embodiment, R 4 is CH3, CF3, Cl or H. In another embodiment, R 2 Selected from the group consisting of:

[0299]

[0300] Formula 9

[0301] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 9. Such compounds are described in the following: International Publication No. WO2021023616A1 published on February 11, 2021 and corresponding to International Application No. PCT / EP2020 / 071514 filed on July 30, 2020; International Publication No. WO2019161877A1 published on August 29, 2019 and corresponding to International Application No. PCT / EP2018 / 054057 filed on February 20, 2018; International Publication No. WO2019161877A1 published on September 8, 2022 and corresponding to International Application No. PCT / EP2018 / 054057 filed on July 30, 2020; U.S. Publication No. US20220280455A1 of U.S. Application No. 17 / 631,762; U.S. Publication No. US20210032196A1, published on February 4, 2021, and corresponding to U.S. Application No. 16 / 943,872, filed on July 30, 2020; U.S. Publication No. US20210032196A1, published on February 4, 2021, and corresponding to U.S. Application No. 16 / 943,872, filed on July 30, 2020;, which are incorporated herein by reference in their entireties. In the event of any conflict in any terminology within the context of Formula 9, these references are incorporated herein by reference for reference only.

[0302] In one embodiment, the Kv7 channel activator is a compound according to Formula 9:

[0303]

[0304] wherein R1 is selected from the group consisting of: C1-C6 alkyl, CF3, CH2CF3, CF2CHF2, C3-C8 cycloalkyl, wherein the C3-C8 cycloalkyl may be substituted with 1 or 2 substituents selected from the group consisting of: C1-C3 alkyl, F, CHF2 and CF3; and R2 is H, C1-C6 alkyl or CF3; or R1 and R2 are combined to form a C3-C5 cycloalkyl optionally substituted with 1 or 2 F, CHF2 or CF3; and R3 is C1-C3 alkyl or CH2O—C 1-3 Alkyl, the C1-C3 alkyl or CH2O-C1-C3 is an alkyl substituted by C≡N, 3F or C3-C5 cycloalkyl; R4 is selected from the group consisting of OCF3 or OCHF2

[0305] In further embodiments, R4 is OCF3 or OCHF2.

[0306] In another embodiment, R3 is selected from the group consisting of CH2—O—CF3, CH2—O-cyclopropyl, and CH2—C≡N.

[0307] In further embodiments, R1 is C3-C4 cycloalkyl optionally substituted with 1 or 2 C1-C3 alkyl, F, CHF2 or CF3.

[0308] In further embodiments, R1 and R2 combine to form cyclobutyl optionally substituted with 1 or 2 F, and R4 is OCF3 or OCHF2.

[0309] In further embodiments, the Kv7 channel activator is selected from the group consisting of: (S)—N—((R)-2-cyclopropyloxy-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (S)—N—((R)-1-(3-(difluoromethoxy)phenyl)-2-(trifluoromethoxy)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (S)—N—((R)-1-(3-(trifluoromethoxy)phenyl)-2-(trifluoromethoxy)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (S)—N—((S)-2-cyano-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide; and (S)—N-(2-cyano-1-(3-(trifluoromethoxy)phenyl)ethyl)-2-(3,3-difluoro-1-hydroxycyclobutyl)acetamide or a pharmaceutically acceptable salt of any of these compounds.

[0310] In further embodiments, the Kv7 channel activator is selected from the group consisting of: (R)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (S)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (S)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide; (R)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-3-(1-(trifluoro-methyl)cyclopropyl)propionamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-3-(1-(trifluoro-methyl)cyclopropyl)propionamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxy-3-(1-(trifluoromethyl)cyclopropyl)propionamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxy-3-(1 -(trifluoromethyl)cyclopropyl)propionamide; (R)-3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxypropionamide; (S)-3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxypropionamide; (R)-3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxypropionamide; (S)-3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxypropionamide (S)-3-(3,3-difluorocyclobutyl)-N—((S)-1-(3-(difluoromethoxy)phenyl)butyl)-3-hydroxypropionamide; (R)-3-(3,3-difluorocyclobutyl)-N—((S)-1-(3-(difluoromethoxy)phenyl)butyl)-3-hydroxypropionamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(1-ethylcyclopropyl)-3-hydroxypropionamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(1-ethylcyclopropyl)-3-hydroxypropionamide;(S)—N—((S)-1-(3-(difluoromethoxy)phenyl)butyl)-3-hydroxy-4,4-dimethylpentanamide; (S)—N—((S)-1-(3-(difluoromethoxy)phenyl)-4,4-difluorobutyl)-3-hydroxy-4,4-dimethylpentanamide; (S)—N—((S)-1-(3-(difluoromethoxy)phenyl)-3,3-difluoropropyl)-3-hydroxy-4,4-dimethylpentanamide; (S)—N—((S)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (R)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N-(2-(difluoromethoxy)-1-(3-(difluoromethoxy) (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(difluoromethoxy)phenyl)butyl)acetamide; (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(difluoromethoxy)phenyl)-4,4-difluorobutyl)acetamide; (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(difluoromethoxy)phenyl)-4,4-difluorobutyl)acetamide; (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(trifluoromethoxy)phenyl)propyl)acetamide; (S)-N-(3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(trifluoromethoxy)phenyl)propyl)acetamide (S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(1-fluorocyclopropyl)-3-hydroxybutanamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(1-fluorocyclopropyl)-3-hydroxybutanamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(1-fluorocyclopropyl)-3-hydroxybutanamide; (1-Fluorocyclopropyl)-3-hydroxybutanamide; (R)-N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(1-fluorocyclopropyl)-3-hydroxybutanamide; (R)-3-Cyclopropyl-N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxybutanamide; (S)-3-Cyclopropyl-N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxybutanamide; (R)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-5,5,5-trifluoro-3-hydroxy-3-methylpentanamide;(S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-5,5,5-trifluoro-3-hydroxy-3-methylpentanamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-3,5-dimethylhexanamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy -3,5-dimethylhexanamide; (S)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-3,4-dimethylpentanamide; (R)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-3,4-dimethylpentanamide; (S)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl) -3-(3,3-dimethylcyclobutyl)-3-hydroxypropionamide; (R)-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(3,3-dimethylcyclobutyl)-3-hydroxypropionamide; (S)-3-cyclopentyl-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxypropionamide; (R)-3-cyclopentyl-N-((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxypropionamide (R)-3-(1-fluorocyclopropyl)-3-hydroxy-N—((R)-2-methoxy-1-(3-(trifluoromethoxy)phenyl)ethyl)butanamide; and (S)-3-(1-fluorocyclopropyl)-3-hydroxy-N—((R)-2-methoxy-1-(3-(trifluoromethoxy)phenyl)ethyl)butanamide; or pharmaceutically acceptable salts of any of these compounds.

[0311] In further embodiments, the Kv7 channel activator is a compound according to Formula 8, wherein R 1 is selected from the group consisting of: C1-C6 alkyl, CF3, CH2CF3, CF2CHF2, C3-C8 cycloalkyl, wherein the C3-C8 cycloalkyl may be substituted with 1 or 2 F, CHF2 or CF3, and R 2 is H, C1-C6 alkyl or CF3; or R 1 and R 2 Combined to form a C3-C5 cycloalkyl group optionally substituted with 1 or 2 F, CHF2 or CF3; R 3 Is C1-C3 alkyl or CH2O-C 1-3 Alkyl, the C1-C3 alkyl or CH2O—C 1-3 The alkyl group may be optionally substituted with 1 or 2 F groups; and R4 Selected from the group consisting of OCF3, OCH2CF3 or OCHF2.

[0312] In another embodiment, R 4 It is OCF3 or OCHF2.

[0313] In another embodiment, R 2 It is H or CH3.

[0314] In another embodiment, R 3 It is CH2O—C 1-3 alkyl.

[0315] In another embodiment, R 1 is C3-C4 cycloalkyl optionally substituted by 1 or 2 F, CHF2 or CF3.

[0316] In another embodiment, R 1 is tert-butyl, and R 2 is H, and R 4 It is OCF3, OCH2CF3, OCHF2 or CF3.

[0317] In another embodiment, R 1 and R 2 to form a cyclobutyl group optionally substituted with 1 or 2 F, and R 4 It is OCF3, OCH2CF3, OCHF2 or CF3.

[0318] In further embodiments, the Kv7 channel activator is selected from the group consisting of: (S)-3-hydroxy-4,4-dimethyl-N-[(1S)-1-[3-(trifluoromethoxy)phenyl]ethyl]pentanamide, (R)-3-hydroxy-4,4-dimethyl-N-[(1S)-1-[3-(trifluoromethoxy)phenyl]ethyl]pentanamide, (S)-3-hydroxy-4,4-dimethyl-N-[(S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide Amide, (R)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide, (S)-N-((S)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide, (R)-N-((S)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide, (S)-3-hydroxy-4,4-dimethyl-N-((S)- 1-(3-(trifluoromethyl)phenyl)ethyl)pentanamide, (R)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethyl)phenyl)ethyl)pentanamide, (S)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)propyl)pentanamide, (R)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)propyl)pentanamide, (S)-3-(3,3-difluoro (S)-1-(3-(trifluoromethoxy)phenyl)ethyl)propionamide, (R)-3-(3,3-difluorocyclobutyl)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)propionamide, (S)-3-hydroxy-4-methyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide, (R)-3-hydroxy-4-methyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide(S)-3-(1-(difluoromethyl)cyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)propanamide, (R)-3-(1-(difluoromethyl)cyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)propanamide, (R)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)propanamide, (R)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(1-(trifluoromethyl)cyclopropyl)propanamide, (S)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(1-(trifluoromethyl)cyclopropyl)propanamide, (S)-3-hydroxy -4-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentanamide, (R)-3-hydroxy-4-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentanamide, N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(R)-hydroxy-4,4-dimethylpentanamide, N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(S)-hydroxy-4,4-dimethylpentanamide, (S)-3-hydroxy-N-((R)-2-methoxy-1-(3-(trifluoromethoxy)phenyl)ethyl)-4,4-dimethylpentanamide, ( R)-3-hydroxy-N-((R)-2-methoxy-1-(3-(trifluoromethoxy)phenyl)ethyl)-4,4-dimethylpentanamide, (S)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(trifluoromethoxy)phenyl)ethyl)acetamide, (S)-2-(1-hydroxycyclobutyl)-N-(1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)acetamide, (3R)-3-hydroxy-4-methyl-N-[(1S)-1-[3-(2,2,2-trifluoroethoxy)phenyl]ethyl]-3-(trifluoromethyl)pentanamide, (3S)-3-hydroxy-4-methyl-N-[(1S)-1-[3-(2,2,2-trifluoroethoxy)phenyl]ethyl]-3-(trifluoromethyl)pentanamide pentylamide, (S)-4,4,5,5-tetrafluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentylamide, (R)-5,5,5-trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentylamide, (S)-5,5,5-tetrafluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentylamide, (R)-5,5,5-trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentylamide, (S)-5,5,5-tetrafluoro-3-hydroxy-3-methyl5-Trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)pentanamide, (R)-3-(1-fluorocyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)butanamide, (S)-3-(1-fluorocyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoro-methoxy)phenyl)ethyl)butanamide, (R)-2-(1-hydroxycyclopentyl)-N-(2-methoxy-1-(3-(trifluoromethoxy)phenyl)ethyl)acetamide, (R)-3-cyclopropyl-3-hydroxy-N-((S) -1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide, (S)-3-cyclopropyl-3-hydroxy-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide, (R)-4,4,4-trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide and (S)-4,4,4-trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide or a pharmaceutically acceptable salt of any of these compounds.

[0319] Formula 10

[0320] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 10. Such compounds are described in: International Publication No. WO2009015667A1 published on February 5, 2009 and corresponding to International Application No. PCT / DK2008 / 050191 filed on July 31, 2008; International Publication No. WO2004058 published on July 15, 2004 and corresponding to International Application No. PCT / DK2003 / 000906 filed on December 18, 2003; No. 739A1, filed on May 6, 2008, corresponding to U.S. application Ser. No. 10 / 540,075, filed on December 18, 2003; U.S. Publication No. US20100256145A1, published on October 7, 2010, corresponding to U.S. application Ser. No. 12 / 671,505, filed on July 31, 2008; each of which is incorporated herein by reference in its entirety. In the event of any conflict in any terminology within the context of Formula 8, these references are hereby incorporated by reference herein for all purposes.

[0321] In one embodiment, the Kv7 channel activator is a compound according to Formula 10:

[0322]

[0323] where R 1 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl) group; R 2 and R 2' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), aryl-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl) group; R 3 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 3-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl), NR 10 R 10' —C 1-4 -Alkyl (ene / yne) group, NR 10 R 10' —C 3-8 -cycloalkyl(enyl) and hydroxy-C 3-8 -cycloalkyl(enyl) group; wherein: R 10 and R 10' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 10 and R 10' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; X is CO or SO2; Z is O or NR 4 , where: R 4 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl) group; or R 3 and R 4 Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms, and R 3 and R 4 and the nitrogen atom to form a ring optionally substituted by one or more independently selected from C 1-6 -alk(en / yn)yl, aryl and aryl-C 1-6 -substituted with a substituent of the alk(en / yn) group; q is 0 or 1; and Y represents a heteroaryl group of one of the following formulae:

[0324]

[0325] Where: W is O or S; m is 0, 1, 2 or 3; n is 0, 1, 2, 3 or 4; p is 0 or 1; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, acyl, halogen, halo-C 1-6 -Alkyl (ene / ynyl) group, alkoxy (ene / ynyl) group, -CO-NR 6 R 6' , cyano, nitro, -NR 7R 4' 、—S—R 8 ,—SO2R 8 and SO2OR 8 ; Among them: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl and aryl; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, aryl and acyl; and R 8 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 1-6 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl) group, aryl and NR 9 R 9' ; Among them: R 9 and R 9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or a pharmaceutically acceptable salt thereof.

[0326] In further embodiments, the Kv7 channel activator is selected from the group consisting of: {2-amino-4-[(5-chloro-thiophen-2-ylmethyl)-methyl-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-methyl-thiophen-2-ylmethyl)-methyl-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-bromo-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(6-chloro-3-methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {(2-amino- 4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-methyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(4-bromo-3-methoxy-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(3-chloro-thiophen-2-ylmethyl-amino]-phenyl}-carbamic acid ethyl ester; (2-amino-4-{[4-(4-chloro-benzenesulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-phenyl)-carbamic acid ethyl ester Ester; {2-amino-4-[(3-methyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-fluoro-benzofuran-3-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(4-bromo-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-ethyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(thiophen-3-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-chloro-thiophene {2-amino-4-[(benzo[b]thiophen-3-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-dimethyl-amino-benzo[b]thiophen-3-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-dimethyl-amino-3-methyl-benzo[b]thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(5-fluoro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(benzo[b]thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester;{2-amino-4-[(benzo[b]thiophen-3-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; N-{2-amino-4-[(5-chloro-thiophen-2-ylmethyl)amino]phenyl}-2-(4-fluoro-phenyl)-acetamide; N-{2-amino-4-[(5-chloro-thiophen-2-ylmethyl)amino]phenyl}-3,3-dimethyl-butyramide; and pharmaceutically acceptable salts thereof. ;

[0327] In further embodiments, the Kv7 channel activator is a compound according to the formula:

[0328]

[0329] or a pharmaceutically acceptable salt thereof.

[0330] In further embodiments, the Kv7 channel activator is selected from the group consisting of: 2-cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-3,3-dimethyl-butyramide; N-(4,6-dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-2-(4-fluoro-phenyl)-acetamide; hexanoic acid (2,6-difluoro-4-morpholin-4-yl-phenyl)-amide; 2-cyclopentyl-N-(4,6- dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-acetamide; N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-propionamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3,3-dimethyl-butyramide; [2-amino-4-(2,4,6-trimethyl-benzylamino)-phenyl]-carbamic acid ethyl ester; 2-cyclopentyl-N-(2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-acetamide; and pharmaceutically acceptable salts thereof.

[0331] In further embodiments, the Kv7 channel activator is a compound according to Formula 10, wherein: R 1 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl) group; R 2 and R 2' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl) group; R 3 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl), NR 10 R 10' —C 1-6 -Alkyl (ene / yne) group, NR 10 R 10' —C 3-8 -cycloalkyl(enyl) and hydroxy-C 3-8 -cycloalkyl(enyl) groups, wherein: R 10 and R 10' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, or R 10 and R 10' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; X is CO or SO2; Z is O or NR 4 , where: R 4 Selected from the group consisting of: hydrogen, C1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl) group; or R 3 and R 4 Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms, wherein R 3 and R 4 and the nitrogen atom to form a ring optionally substituted by one or more independently selected from C 1-6 -alk(en / yn)yl, aryl and aryl-C 1-6 -substituted with a substituent of the alk(en / yn) group; q is 0 or 1; and Y represents a heteroaryl group of the formula:

[0332]

[0333] Where: W is S; m is 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; p is 0 or 1; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, acyl, halogen, halo-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, -CO-NR 6 R 6' , cyano, nitro, -NR 7 R 7' 、—S—R 8 ,—SO2R 8 and SO2OR 8 , where: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl and aryl; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8-cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, aryl and acyl; and R 8 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl and -NR 9 R 9' , where: R 9 and R 9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or a pharmaceutically acceptable salt thereof.

[0334] In another embodiment, R 1 Selected from hydrogen and C 1-6 - a group consisting of alk(en / yn) groups.

[0335] In other embodiments, the substituent R 2 and R 2' At least one substituent is a hydrogen atom.

[0336] In another embodiment, R 2 and R 2' Both are hydrogen atoms.

[0337] In further embodiments, X is CO.

[0338] In another embodiment, q is 0.

[0339] In further embodiments, q is 1, and Z is an oxygen atom.

[0340] In another embodiment, R 3 Choose from C 1-6 -Alk(en / yn)yl and aryl-C 1-6 - a group consisting of alk(en / yn) groups.

[0341] In another embodiment, R 3 It is C 1-6 -alk(en / yn)yl.

[0342] In another embodiment, R 3 is aryl-C 1-6 -alk(en / yn)yl.

[0343] In further embodiments, W is a sulfur atom.

[0344] In further embodiments, Y has the formula:

[0345]

[0346] Where: W is S; m is 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; p is 0 or 1; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, acyl, halogen, halo-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, -CO-NR 6 R 6' , cyano, nitro, -NR 7 R 7' 、—S—R 8 ,—SO2R 8 and SO2OR 8 , where: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl and aryl; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, aryl and acyl; and R 8 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl and -NR 9 R 9' , where: R 9 and R 9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl.

[0347] In further embodiments, Y has the formula:

[0348]

[0349] Where: W is S; m is 0, 1, 2, or 3; n is 0, 1, 2, 3, or 4; p is 0 or 1; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), aryl, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, acyl, halogen, halo-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, -CO-NR 6 R 6' , cyano, nitro, -NR 7 R 7' 、—S—R 8 ,—SO2R 8 and SO2OR 8 , where: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl and aryl; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, aryl and acyl; and R 8 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl and -NR 9 R 9' , where: R 9 and R 9'independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl.

[0350] Formula 11

[0351] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 11. Such compounds are described in the following: International Publication No. WO2009015667A1, published on February 5, 2009, corresponding to International Application No. PCT / DK2008 / 050191, filed on July 31, 2008; International Publication No. WO2004058739A1, published on July 15, 2004, corresponding to International Application No. PCT / DK2003 / 000906, filed on December 18, 2003; U.S. Patent No. 7,368,472, issued on May 6, 2008, corresponding to U.S. Application No. 10 / 540,075, filed on December 18, 2003;

[0014] The present invention relates to U.S. Patent Application No. 12 / 671,505, filed on July 31, 2008, U.S. Publication No. US20100256145A1, published on October 7, 2004, and corresponding to U.S. Application No. 12 / 671,505, filed on July 31, 2008; International Publication No. WO2004082677A1, published on September 30, 2004, and corresponding to International Application No. PCT / DK2004 / 000186, filed on March 18, 2004; and International Publication No. WO2004080950A1, published and issued on September 23, 2004, and corresponding to International Application No. PCT / DK2004 / 000162, filed on March 12, 2004; each of which is incorporated herein by reference in its entirety. In the event of any conflict in the context of Formula 11, these references are incorporated herein by reference.

[0352] In one embodiment, the Kv7 channel activator is a compound according to Formula 11:

[0353]

[0354] Where: s is 0 or 1; U is O, S, SO2, SO2NR 11 , CO—O or CONR 11 ; Among them: R 11 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8-cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 2 and R 11 With R 11 The nitrogen atoms to which they are attached together form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; q is 0 or 1; X is CO or SO2; provided that when X is SO2, then q is 0; Z is O or S; R 1 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; R 2 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6-alk(ene / ynyl), cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 10 R 10' —C 1-6 -Alkyl (ene / yne) group, NR 10 R 10' —C 3-8 -cycloalkyl (alkenyl) and NR 10 R 10' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein R 10 and R 10' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alkane (alkenyl / group, or R 10 and R 10' Together with the nitrogen atom to which it is attached, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; and provided that: when R 2 is halogen or cyano, then s is 0; and when s is 1 and R 2 When it is a hydrogen atom or an acyl group, U is O or S; R 3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), heterocycloalkyl (alkenyl), C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alk(ene / ynyl)-heterocycloalkyl(ene)-, heterocycloalkyl(ene)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar-heterocycloalkyl (alkenyl), Ar-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), Ar—C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 3-8 -cycloalkyl(enyl) group, C 1-6 -alk(ene / ynyl)oxy-heterocycloalk(ene)yl, Ar-oxy-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-heterocycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl (alkenyl), halogenated heterocycloalkyl (alkenyl), halogenated-C 3-8-cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 1-6 -Alk(ene / ynyl)-Ar, halo-C 3-8 -cycloalkyl (alkenyl)-Ar, halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl) -Ar, halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (enyl)-Ar, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-heterocycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), cyano-C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, acyl -C 1-6 -alk(ene / ynyl), acyl-C 3-8 -cycloalkyl (enyl), acyl-heterocycloalkyl (enyl), acyl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl) group, acyl-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, NR 12 R 12' , optionally substituted NR 12 R 12' —C 1-6 -alk(en / yn)yl, optionally substituted NR 12 R 12' —C 3-8 -cycloalkyl(en)yl and optionally substituted NR 12 R 12' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein: R 12 and R 12' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar-heterocycloalk(ene), Ar-oxy-C 1-6 -alk(ene / ynyl), Ar-oxy-C 3-8 -cycloalkyl(enyl) group, Ar-oxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, Ar-oxy-heterocycloalk(ene) group, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 12 and R 12' Together with the nitrogen atom to which it is attached, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that: when R 3 It is NR 12 R 12' When , q is 0; and Y represents a set of the following formulas:

[0355]

[0356] wherein: the line represents a bond connecting the group represented by Y to a carbon atom; W is O or S; V is N, C, or CH; T is N, NH, or O; a is 0, 1, 2, or 3; b is 0, 1, 2, 3, or 4; c is 0 or 1; d is 0, 1, 2, or 3; e is 0, 1, or 2; f is 0, 1, 2, 3, 4, or 5; g is 0, 1, 2, 3, or 4; h is 0, 1, 2, or 3; j is 0, 1, or 2; k is 0, 1, 2, or 3; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8-cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, Ar-oxy, Ar-oxy-C 1-6 -alk(ene / ynyl), Ar-oxy-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alk(ene / yn)yl-heterocycloalk(ene)yl, Ar-oxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, C 1-6 -alk(en / yn)yloxy-carbonyl, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, -CO-NR 6 R 6' , cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 7 R 7' 、S—R 8 and SO2R 8 ; or two adjacent R 5 Together with the aromatic group, it forms a 5-8 membered ring optionally containing one or two heteroatoms; wherein: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group and Ar; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8-cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl), Ar, heterocycloalkyl (ene) -C 1-6 -Alkyl (ene / alkynyl), heterocycloalkyl (ene) -C 3-8 -cycloalkyl (enyl) group, heterocycloalkyl (enyl) group-C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, heterocycloalk(en)yl-Ar and acyl; or R 7 and R 7' Together with the nitrogen atom to which it is attached, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; and R 8 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar and -NR 9 R 9' ; where R 9 and R 9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or a pharmaceutically acceptable salt thereof.

[0357] In further embodiments, the Kv7 channel activator is selected from the group consisting of: {4-[(benzofuran-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid ethyl ester; {4-[(benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid ethyl ester; {2-methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; [4-(4-isopropyl-benzylamino)-2-methylphenyl]-carbamic acid ethyl ester; [4-(4-fluoro-benzylamino)-2-methylphenyl]-carbamic acid propyl ester; (4-{[4-(4-chloro- -phenylsulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino}-2-methylphenyl)-carbamic acid propyl ester; {4-[(5-methyl-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; {2-methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; [4-(4-isopropyl-benzylamino)- 2-Methylphenyl]-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid ethyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid ethyl ester; {4-[(benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid ethyl ester; [2-chloro-4-(4-isopropyl-benzylamino)-phenyl]-carbamic acid ethyl ester; [2-chloro-4-(4-fluoro-benzylamino)-phenyl]-carbamic acid propyl ester; 2-chloro-4-{[4-(4-chloro-phenylsulfonyl)-3-methyl-thiophen-2-ylmethyl]-amino)-phenyl}-carbamic acid propyl ester; {4-[(5-methyl-thiophen-2 -ylmethyl)-amino]-2-chlorophenyl}-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid propyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid propyl ester; {4-[(Benzofuran-2-ylmethyl)-amino]-2-chlorophenyl}-carbamic acid propyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-carbamic acid ethyl ester; {4-[(Benzo[b]thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-carbamic acid methyl ester;{4-[(5-Bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-carbamic acid isopropyl ester; {4-[(4-Fluoro-benzyl)-(methyl)amino]-2-methoxyphenyl}-carbamic acid propyl ester; [4-(Benzo[b]thiophen-2-ylmethyl-(methyl)amino)-2-methoxy-phenyl]-carbamic acid propyl ester; {4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamic acid propyl ester; {4-[(5-Bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamic acid propyl ester; {2-methoxy-4-[methyl-(5-methyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl carbamate; {4-[(4-fluorobenzyl)-(methyl)-amino]-2-isopropoxyphenyl}-carbamic acid ethyl ester; [4-(3-fluorobenzylamino)-2-methoxyphenyl]-carbamic acid ethyl ester; [4-(4-isopropylbenzylamino)-2-methoxyphenyl]-carbamic acid ethyl ester; {2-methoxy-4-[(3-methylthiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester; [4-(2,4-difluorobenzylamino)-2-methoxyphenyl]-carbamic acid ethyl ester; [2-cyclopentyloxy-4-(4-methoxybenzylamino)-phenyl]-carbamic acid ethyl ester; [2-cyclopentyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamic acid ethyl ester; [4-(3-fluoro-2- [2-Benzyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamic acid ethyl ester; [2-Benzyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamic acid ethyl ester; [2-Benzyloxy-4-(4-methylthiobenzylamino)-phenyl]-carbamic acid ethyl ester; {4-[(Benzo[b]thiophen-3-ylmethyl)-amino]-2-cyclopentyloxyphenyl}-carbamic acid ethyl ester; [4-(3-fluoro-2-methylbenzylamino)-2-isopropoxyphenyl]-carbamic acid ethyl ester; [2-Benzyloxy-4-(3-methoxybenzylamino)-phenyl]-carbamic acid ethyl ester; {4-[(Benzo[1,3]dioxolan-5-ylmethyl)-amino]-2-isopropoxyphenyl}-carbamic acid ethyl ester; {4-[(5 {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; [2-cyano-4-(4-isopropylbenzylamino)-phenyl]-carbamic acid ethyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-carbamic acid propyl ester; {4-[(4-isopropylbenzyl)-(methyl)amino]-2-methylphenyl}-carbamic acid propyl ester; {2-methyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester; {2-methyl-4-[methyl-(4-methylthio-benzyl)-amino]-phenyl}-carbamic acid propyl ester;{4-[(4-tert-Butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-carbamic acid ethyl ester; {2-chloro-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid ethyl ester; {2-chloro-4-[methyl-(4-methylthio-benzyl)-amino]-phenyl}-carbamic acid ethyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-chlorophenyl}-carbamic acid propyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester; {4-[(4-tert-Butyl-benzyl)-(methyl)amino]-2-chlorophenyl}-carbamic acid propyl ester; {2-chloro-4-[methyl-( {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[(4-isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[methyl -(4-methylthio-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; {4-[(4-isopropyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; {4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; {4-[methyl-(4-trifluoromethyl-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid Propyl ester; {4-[methyl-(4-methylthio-benzyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-2-cyanophenyl}-carbamic acid propyl ester; {4-[(4-tert-butyl-benzyl)-(methyl)amino]-2-cyanophenyl}-carbamic acid propyl ester; {2-cyano-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester; {2-bromo-4-[(5-bromo-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester; {2-bromo-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester;{2-bromo-4-[(4-isopropylbenzyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester; {2-bromo-4-[(4-tert-butyl-benzyl)-(methyl)amino]-phenyl}-carbamic acid propyl ester; {2-bromo-4-[methyl-(4-trifluoromethyl-benzyl-amino]-phenyl}-carbamic acid propyl ester; [2-iodo-4-(4-isopropyl-benzylamino)-phenyl]-carbamic acid propyl ester; [4-(4-tert-butyl-benzylamino)-2-iodophenyl]-carbamic acid propyl ester; [2-iodo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester; [2-iodo-4-(4-methylthio-benzylamino)-phenyl]-carbamic acid propyl ester; {2-iodo- 4-[4-(4-Methylpiperazin-1-yl)-benzylamino]-phenyl}-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid ethyl ester; [4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid ethyl ester; [4-(4-methylthio-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid ethyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-trifluoromethyl-phenyl}-carbamic acid propyl ester; [4-(4-isopropylbenzylamino)-2-trifluoromethyl-phenyl [4-(4-tert-butyl-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester; [2-trifluoromethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester; [4-(4-dimethylamino-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester; [4-(4-methylthio-benzylamino)-2-trifluoromethyl-phenyl]-carbamic acid propyl ester; {4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-carbamic acid propyl ester; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-cyanophenyl}-carbamic acid propyl ester; [2-cyano-4-(4-trifluoromethyl-benzylamino)-phenyl [2-Bromo-4-[(5-bromo-thiophen-2-ylmethyl)-amino]-phenyl]-carbamic acid propyl ester; [2-Bromo-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; [2-Bromo-4-(4-isopropylbenzylamino)-phenyl]-carbamic acid propyl ester; [2-Bromo-4-(4-tert-butyl-benzylamino)-phenyl]-carbamic acid propyl ester; [2-Bromo-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester; [2-Bromo-4-(4-methylthio-benzylamino)-phenyl]-carbamic acid propyl ester; N-{4-[(5-bromo-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butyramide;N-{4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-methoxyphenyl}-butyramide; N-[4-(4-isopropylbenzylamino)-2-methoxyphenyl]-butyramide; N-[4-(4-tert-butyl-benzylamino)-2-methoxyphenyl]-butyramide; N-[2-methoxy-4-(4-trifluoromethyl-benzylamino)-phenyl]-butyramide; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-furan-2-yl-phenyl}-carbamic acid propyl ester; [2-furan-2-yl-4-(4-isopropylbenzylamino)-phenyl]-carbamic acid propyl ester; [5-(4-fluorobenzylamino)-biphenyl-2-yl]-carbamic acid propyl ester; {5-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-furan-2-yl-phenyl}-carbamic acid propyl ester [5-(4-Isopropylbenzylamino)-biphenyl-2-yl]-carbamic acid propyl ester; [5-(4-isopropylbenzylamino)-biphenyl-2-yl]-carbamic acid propyl ester; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-phenylacetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3,3-dimethylbutanamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-phenylpropanamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-butanamide; valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-butanamide phenyl}-amide; cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide; cyclobutanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide; cyclopentanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide; cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-amide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-thiophen-2-yl-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-thiophen-2-yl-acetamide; -[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(3-methoxy-phenyl)-acetamide, N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl)-2-(4-chloro-phenyl}-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-methoxy-phenyl)-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl)-2-(4-fluoro-phenyl}-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-cyclohexylpropionamide;N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2-dimethylpropanamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenoxyacetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-phenylacetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3,3-dimethylbutanamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-butanamide; valeric acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide Cyclopropanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide; Cyclobutanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide; Cyclopentanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide; Cyclohexanecarboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-thiophen-2-yl-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(3-methoxyphenyl)-1,2-di ... N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-chlorophenyl)-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-methoxyphenyl)-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2-(4-fluorophenyl)-acetamide; 2,3-dihydro-benzo[1,4]dioxin-6-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide; 2,3-dihydro-benzofuran-5-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl) -amino]-phenyl}-amide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3-cyclohexylpropionamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2,2-dimethylpropionamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2-phenylacetamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3,3-dimethylbutanamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3-phenylpropionamide;N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-butyramide; 2,2,2-trichloro-N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-acetamide; cyclopropanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-amide; cyclobutanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide; cyclopentanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide; cyclohexanecarboxylic acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide -ylmethyl)-(methyl)amino]-2-methylphenyl}-amide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-thiophen-2-yl-acetamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(3-methoxyphenyl)-acetamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-malonamic acid methyl ester; 2-(4-chlorophenyl)-N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-acetamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-acetamide phenyl}-2-(4-methoxyphenyl)-acetamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide; N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-3-cyclohexylpropionamide; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid phenyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid benzyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid benzyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid isobutyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid butyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid hexyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 4-nitrobenzyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid but-3-enyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid but-2-ynyl ester;{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2,2-dimethylpropyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-chlorobenzyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 3-chloropropyl ester; {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-carbamic acid 2-benzyloxyethyl ester; 3-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-1-methyl-1-propyl-urea; 1-{2-chloro-4-[(5 -chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3-(2-fluorophenyl)-urea; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2-trifluoroacetamide; N-{5-[(5-chloro-thiophen-2-ylmethyl)-amino]-4'-dimethylamino-biphenyl-2-yl}-2-(4-fluorophenyl)-acetamide; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chlorophenyl)-acetamide; [4-(3-fluoro-4- Ethyl trifluoromethyl-benzylamino)-2-methylphenyl]-carbamate; 2-(4-fluorophenyl)-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-acetamide; N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-butyramide; 2-(4-fluorophenyl)-N-{2-methyl-4-[6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-acetamide; valeric acid {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methylphenyl}-amide; 3,3-dimethyl-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-butyramide; [2- Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid ethyl ester; N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2-(4-chlorophenyl)-propionamide; [4-(4-chloro-benzylamino)-2-methylphenyl]-carbamic acid ethyl ester; {4-[(6-methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; {4-[(5=chloro-thiophen-2-ylmethyl)-amino]-2-quinolin-3-yl-phenyl}-carbamic acid ethyl ester; {4-[(5-dimethylamino-3-methyl-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester;3,3-Dimethyl-N-{2-methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-butyramide; N-(4-{[6-(4-cyanophenoxy)-pyridin-3-ylmethyl]-amino}-2-methylphenyl)-2-(4-fluorophenyl)-acetamide; S-ethyl {2-benzyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamate; S-ethyl {2-cyclopentyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamate; N-{4-[(6-chloropyridin-3-ylmethyl)-amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide; {4-[(7-dimethylamino- Benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; 1-{2-cyclopentyloxy-4-[(4-fluorobenzyl)-(methyl)amino]-phenyl}-3-ethyl-urea; 2-amino-4-methyl-pentanoic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide; {4-[(6-methoxy-benzo[b]thiophen-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid ethyl ester; 2-amino-4-methyl-pentanoic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide; 2-(4-fluorophenyl)-N-{2-methyl-4-[(4-methyl-2-phenylpyrimidin-5-ylmethyl)-amino]-phenyl}-acetamide, 3,3-dimethyl-N-{2-methyl-4-[(2-phenylpyrimidin-5-ylmethyl)-amino]-phenyl}-butyramide; ethyl {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-3-yl-phenyl}-carbamate; 1-amino-cyclopropanecarboxylic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide; ethyl {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-4-yl-phenyl}-carbamate; N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-piperidin-1-yl-acetamide; N-(4-{[5-(4-chlorophenoxy)-1,3-dimethyl-1H- [4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-(6-methoxypyridin-3-yl)-phenyl]-carbamic acid ethyl ester; 4-[(3-methyl-4-propoxycarbonylamino-phenylamino)-methyl]-benzoic acid methyl ester; N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-morpholin-4-yl-acetamide;2,2-Dimethyl-N-{2-methyl-4-[(3-methyl-5-phenylisoxazol-4-ylmethyl)-amino]-phenyl}-propionamide; {4-[(5-chloro-thiophen-2-ylmethyl-amino]-2-iodophenyl}-carbamic acid ethyl ester; N-{4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-iodophenyl}-2-(4-fluorophenyl)-acetamide; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2-quinolin-5-yl-phenyl}-carbamic acid ethyl ester; and pharmaceutically acceptable salts thereof.

[0358] In another embodiment, the Kv7 channel activator is a compound according to formula 11, wherein: s is 0 or 1; U is O, S, SO2, SONR 11 or CONR 11 ; Among them: R 11 It is hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) or C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 2 and R 11 Together with the nitrogen atom, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; q is 0 or 1; X is CO or SO2; provided that when X is SO2, q is 0; Z is O or S; R 1 It is hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (enyl) or cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; R 2 It is hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8-cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 10 R 10' —C 1-6 -Alkyl (ene / yne) group, NR 10 R 10' —C 3-8 -cycloalkyl (enyl) or NR 10 R 10' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein R 10 and R 10' are independently hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (enyl) or cyano-C3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, or R 10 and R 10' Together with the nitrogen atom, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that: when R 2 is halogen or cyano, then s is 0; and when s is 1 and R 2 When it is a hydrogen atom or an acyl group, U is O or S; R 3 It is C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), heterocycloalkyl (alkenyl), C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alk(ene / ynyl)-heterocycloalkyl(ene)-, heterocycloalkyl(ene)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alk(ene / ynyl)oxy-heterocycloalk(ene)yl, C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-heterocycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 3-8 -cycloalkyl (alkenyl), halogenated heterocycloalkyl (alkenyl), halogenated-C 3-8-cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -Alk(ene / ynyl)-heterocycloalk(ene)-, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-heterocycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), cyano-C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, acyl -C 1-6 -alk(ene / ynyl), acyl-C 3-8 -cycloalkyl (enyl), acyl-heterocycloalkyl (enyl), acyl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl) group, acyl-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, NR 12 R 12' , optionally substituted NR 12 R 12' -C 1-6 -alk(en / yn)yl, optionally substituted NR 12 R 12' -C 3-8 -alk(en / yn)yl or optionally substituted NR 12 R 12' -C 3-8 -alk(en / yn)yl-C 1-6 -alk(en / yn)yl; wherein: R 12 and R 12' are independently hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar-heterocycloalk(ene), Ar-oxy-C 1-6-alk(ene / ynyl), Ar-oxy-C 3-8 -cycloalkyl(enyl) group, Ar-oxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, Ar-oxy-heterocycloalk(ene) group, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (enyl) or cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 12 and R 12' Together with the nitrogen atom, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that: when R 3 It is NR 12 R 12' When , q is 0; and Y is a set of the following formulas:

[0359]

[0360] wherein: "|" represents a bond connecting the group represented by Y to a carbon atom; V is C or CH; and k is 0, 1, 2 or 3; and each R 5 Independently C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, Ar-oxy, Ar-oxy-C 1-6 -alk(ene / ynyl), Ar-oxy-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alk(ene / yn)yl-heterocycloalk(ene)yl, Ar-oxy-C 3-8 -cycloalkyl(enyl)-C 1-6-alk(ene / ynyl), acyl, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, C 1-6 -alk(en / yn)yloxy-carbonyl, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, -CO-NR 6 R 6' , cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 7 R 7' 、S—R 8 or SO2R 8 ; or two adjacent R 5 The group together with the aromatic group forms a 5-8 membered ring optionally containing one or two heteroatoms; wherein: R 6 and R 6' are independently hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group or Ar; R 7 and R 7' are independently hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl), Ar, heterocycloalkyl (ene) -C 1-6 -Alkyl (ene / alkynyl), heterocycloalkyl (ene) -C 3-8 -cycloalkyl (enyl) group, heterocycloalkyl (enyl) group-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, heterocycloalk(en)yl-Ar or acyl; or R 7 and R 7' Together with the nitrogen atom, it forms a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; and R 8 It is hydrogen, C 1-6 -alk(ene / ynyl) group, C3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar or -NR 9 R 9' ; Among them: R 9 and R 9' are independently hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) or C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or a salt thereof.

[0361] In another embodiment, R 1 It is C 1-6 - an alk(en / yn) group or a hydrogen atom.

[0362] In further embodiments, s is 0.

[0363] In another embodiment, s is 1.

[0364] In further embodiments, U is an oxygen atom.

[0365] In another embodiment, R 2 It is hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), Ar, Ar—C 1-6 -alk(en / yn)yl, halogen, halo-C 1-6 -alk(ene / ynyl) or cyano; provided that when R 2 is halogen or cyano, then s is 0; and when s is 1 and R 2 When it is a hydrogen atom, U is O or S.

[0366] In further embodiments, Z is an oxygen atom.

[0367] In further embodiments, Z is a sulfur atom.

[0368] In another embodiment, q is 0.

[0369] In another embodiment, q is 1.

[0370] In further embodiments, X is CO.

[0371] In another embodiment, R 3 It is C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6-Alkyl (ene / alkynyl), heterocycloalkyl (ene) -C1 -6 -alk(ene / ynyl), heterocycloalk(ene), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar-oxy-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl), halo-C 1-6 -Alkyl (ene / yne) group, NR 12 R 12' , optionally substituted NR 12 R 12' —C 1-6 -alk(en / yn)yl or optionally substituted NR 12 R 12' —C 3-8 -cycloalkyl(en)yl.

[0372] In another embodiment, R 12 and R 12' are independently hydrogen, C 1-6 -alk(en / yn)yl or Ar.

[0373] In further embodiments, V is CH.

[0374] In another embodiment, each R 5 Independently C 1-6 -alk(ene / ynyl) group, C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, Ar, C 1-6 -alk(en / yn)yloxy, Ar-oxy, C 1-6 -alk(en / yn)yloxy-carbonyl, halogen, halo-C 1-6 -Alkyl (ene / yne) group, NR 7 R 7' 、S—R 8 or SO2R 8 ; or two adjacent R 5 The group together with the aromatic group forms a 5-8 membered ring optionally containing one or two heteroatoms.

[0375] In another embodiment, R 7 and R 7' Both are C 1-6 -alk(en / yn)yl.

[0376] In another embodiment, R 8 It is C 1-6 -alk(en / yn)yl or Ar.

[0377] In further embodiments, the Kv7 channel activator is selected from the group consisting of: 2-(4-fluorophenyl)-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-acetamide; 2-(4-fluorophenyl)-N-{2-methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-acetamide; 3,3-dimethyl-N-{2-methyl-4-[(6-p-tolyloxypyridin-3-ylmethyl)-amino]-phenyl}-butyramide; 3,3-dimethyl-N-{2 -methyl-4-[(6-trifluoromethylpyridin-3-ylmethyl)-amino]-phenyl}-butyramide; N-(4-{[6-(4-cyanophenoxy)-pyridin-3-ylmethyl]-amino}-2-methylphenyl)-2-(4-fluorophenyl)-acetamide; N-{4-[(6-chloropyridin-3-ylmethyl)-amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide; or 2,2-dimethyl-N-{2-methyl-4-[(6-phenoxypyridin-3-ylmethyl)-amino]-phenyl}-propionamide; or a salt thereof.

[0378] In further embodiments, the Kv7 channel activator is a compound according to Formula 11, wherein: U is O, S or NR 2' ; s is 0 or 1; X is CO or SO2; Z is O, S or NR 4 ; where R 4 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl(enyl); q is 0 or 1; R 1 and R 1' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(en / yn)yl and halo-C 3-8 -cycloalkyl(enyl) group; R 2 Selected from the group consisting of: hydrogen, halogen, C 1-6 -alk(ene / ynyl) group, C 3-8-cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl (enyl) group and cyano group; provided that: when R 2 is halogen or cyano, then s is 0; and when s is 1 and U is NR 2' When R 2' Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(en / yn)yl and halo-C 3-8 -cycloalkyl(enyl) group; or R 2 and R 2' together form a 5-8 membered saturated or unsaturated ring optionally containing one additional heteroatom; R 3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(en / yn)yl and halo-C 3-8 -cycloalkyl(en)yl; and Y represents a group of the following formula:

[0379]

[0380] wherein: the line represents the bond connecting the group represented by Y to the nitrogen atom; W is O or S; a is 0, 1, 2, or 3; b is 0, 1, 2, 3, or 4; c is 0 or 1; d is 0, 1, 2, or 3; e is 0, 1, or 2; f is 0, 1, 2, 3, 4, or 5; g is 0, 1, 2, 3, or 4; h is 0, 1, 2, or 3; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl), Ar, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(ene / ynyl), acyl, C 1-6 -alkane (hydrocarbon / alkene / ynyl) oxy, halogen, halogenated-C 1-6 -Alkyl (ene / yne) group, -CO-NR 6 R 6' , cyano, nitro, -NR 7 R 7' 、—S—R 8 and SO2OR 8 ; or two adjacent R 5 The substituents together with the aromatic group form a 5-8 membered saturated or unsaturated ring optionally containing one or two heteroatoms; wherein: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group and Ar; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, Ar and acyl; and R 8 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar and -NR 9 R 9' ; where R 9 and R 9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8-cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl); provided that; when R 5 It is SO2OR 8 When R 8 No—NR 9 R 9' ; and when R 5 It is SO2R 8 When R 8 is not a hydrogen atom; or a pharmaceutically acceptable salt thereof; provided that the compound of formula I is not: N-[4-[[(4-aminophenyl)amino]methyl]phenyl]-acetamide; N-[4-[[(4-amino-2-methylphenyl)amino]methyl]phenyl]-acetamide; N-[4-[[(4-amino-3-methylphenyl)amino]methyl]phenyl]-acetamide; 2-[[[4-(acetylamino)phenyl]methyl]amino]-5-chloro-N-(5-chloro-2-pyridyl)-benzamide; N-[4-[[(3,4,5-trimethoxyphenyl)amino]methyl]phenyl]-acetamide; N-[4-[[(5,6,7,8-tetramethylphenyl)amino]methyl]phenyl]-acetamide;

[0015] N-[4-[[[3-(1H-imidazol-1-ylmethyl)phenyl]amino]methyl]phenyl]-acetamide;

[0016] N-[4-[[[2-(1H-imidazol-1-ylmethyl)phenyl]amino]methyl]phenyl]-acetamide;

[0017] N-[4-[[(4-amino-3,5-dichlorophenyl)amino]methyl]phenyl]-acetamide;

[0018] N-[4-[[(2,4-diamino-6-quinazolinyl)amino]methyl]phenyl]-acetamide; or

[0019] N-[4-[[(2,4-diamino-6-quinazolinyl)amino]methyl]phenyl]-acetamide.

[0381] In another embodiment, R 1 and R 1 'Independently selected from hydrogen and C 1-6 - a group consisting of alk(en / yn) groups.

[0382] In another embodiment, R 1 and R 1 ' is a hydrogen atom.

[0383] In another embodiment, s is 1.

[0384] In further embodiments, s is 0.

[0385] In another embodiment, R 2 Selected from the group consisting of: hydrogen, C 1-6 -alk(en / yn)yl, Ar and halogen, with the proviso that when R is halogen, then s is 0.

[0386] In another embodiment, U ground NR 2 ', and R and R 2 ' is a hydrogen atom.

[0387] In another embodiment, R 2 and R 2 Both are hydrogen atoms.

[0388] In further embodiments, X is CO.

[0389] In another embodiment, q is 0.

[0390] In another embodiment, q is 1.

[0391] In further embodiments, Z is an oxygen atom.

[0392] In another embodiment, R 3 It is C 1-6 -alk(en / yn)yl.

[0393] In another embodiment, each R 5 Independently selected from the group consisting of: C 1-6 -alk(enyne) group, C 3-8 -cycloalkyl (alkenyl), Ar, cyano, halogen, halo-Cι -6 -alk(en / yn) groups and C 1-6 -alk(alkyl / en / yn)yloxy or two adjacent substituents together form a 5-8 membered saturated or unsaturated ring optionally containing one or two heteroatoms.

[0394] In further embodiments, the Kv7 channel activator is selected from the group consisting of: {2-amino-4-[(4-tert-butylphenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; (2-amino-4-phenylaminomethyl-phenyl)-carbamic acid ethyl ester; [2-amino-4-(naphthalen-2-ylaminomethyl)-phenyl]carbamic acid ethyl ester; [2-amino-4-(p-tolylamino-methyl)-phenyl]carbamic acid ethyl ester; {2-amino-4-[(4-trifluoromethylphenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(4-chlorophenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; {2-amino-4-[(3-fluorophenylamino)-methyl]-phenyl}-ethyl carbamate; {2-amino-4-[(4-fluorophenylamino)-methyl]-phenyl}-ethyl carbamate; {2-amino-4-[(2-fluorophenylamino)-methyl]-phenyl}-ethyl carbamate; [2-amino-4-(biphenyl-4-ylaminomethyl)-phenyl]-ethyl carbamate; {2-amino-4-[(2,4-difluorophenylamino)-methyl]-phenyl}-ethyl carbamate; {2-amino-4-[(4-methoxyphenylamino)-methyl]-phenyl}-ethyl carbamate; {2-amino-4-[(4-cyclohexylphenylamino)-methyl]-phenyl}-ethyl carbamate; [2-amino-4-(indan-5-ylaminomethyl-phenyl]-aminomethyl Ethyl carbamate; ethyl {2-amino-4-[(4-isopropylphenylamino)-methyl]-phenyl}-carbamate; ethyl {2-amino-4-[(4-butylphenylamino)-methyl]-phenyl}-carbamate; ethyl {2-amino-4-[(4-chloro-3-fluorophenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(2,4-dichlorophenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(2,3-dichlorophenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(3,5-dichlorophenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(3,4-dichlorophenylamino)methyl]phenyl}carbamate Ester; ethyl {2-amino-4-[(3-trifluoromethylphenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(3-fluoro-4-trifluoromethylphenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(3,4-dichlorophenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(4-cyanophenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(4-fluoro-3-trifluoromethylphenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(3-chloro-4-methylphenylamino)methyl]phenyl}carbamate; ethyl {2-amino-4-[(3-chlorophenylamino)methyl]phenyl}carbamate;[2-amino-4-(m-toluaminomethyl)phenyl]carbamate; ethyl {2-amino-4-[1-(4-chlorophenylamino)ethyl]phenyl}carbamate; ethyl {2-amino-4-[1-(4-trifluoromethylphenylamino)ethyl]phenyl}carbamate; ethyl N-{2-amino-4-[(3-fluorophenylamino)methyl]phenyl}-2,2-dimethylpropionamide; ethyl {4-[(4-chlorophenylamino)methyl]phenyl}carbamate; ethyl {4-[(4-trifluoromethylphenylamino)methyl]phenyl}carbamate; ethyl {4-[(4-chlorophenylamino)methyl]phenyl}carbamate; ethyl {4-[(4-fluorophenylamino)methyl]-2-methylphenyl}carbamate; {4 -[(4-chlorophenylamino)methyl]-2-methylphenyl}carbamate; ethyl {2-methyl-4-[(4-trifluoromethylphenylamino)methyl]phenyl}carbamate; ethyl {4-[(3,4-difluorophenylamino)methyl]-2-methylphenyl}carbamate; ethyl {4-[(3-fluorophenylamino)methyl]-2-methylphenyl}carbamate; ethyl {2-chloro-4-[(4-chlorophenylamino)methyl]phenyl}carbamate; ethyl {2-chloro-4-[(4-trifluoromethyl-phenylamino)methyl]phenyl}-carbamate; ethyl {2-chloro-4-[(4-fluorophenylamino)methyl]phenyl}-carbamate; ethyl {2-chloro-4-[(4-fluorophenylamino)methyl]phenyl}-carbamate; ethyl {2-chloro-4-[(3-fluorophenylamino)methyl]phenyl}amino Ethyl {2-chloro-4-[(3,4-dichlorophenylamino)methyl]phenyl}carbamate; Ethyl {2-chloro-4-[(4-chloro-3-fluorophenylamino)methyl]phenyl}carbamate; Ethyl {4-[(4-chlorophenylamino)methyl]-2-fluorophenyl}carbamate; Ethyl {4-[(4-chloro-3-fluorophenylamino)methyl]-2-fluorophenyl}carbamate; Ethyl {2-fluoro-4-[(4-trifluoromethylphenylamino)methyl]phenyl}carbamate; Ethyl {4'-dimethylamino-5-[(3-fluorophenylamino)methyl]biphenyl-2-yl}carbamate; Ethyl {4'-dimethylamino-5-[(4-trifluoromethylphenylamino)methyl]biphenyl-2-yl}carbamate Ethyl ester; ethyl {4'-chloro-5-[(3-fluorophenylamino)methyl]biphenyl-2-yl}carbamate; ethyl {4'-chloro-5-[(4-trifluoromethylphenylamino)methyl]biphenyl-2-yl}carbamate; N-{4-[(4-chlorophenylamino)methyl]phenyl}butanamide; N-{4-[(3,4-dichlorophenylamino)methyl]phenyl}butanamide; N-{4-[(4-chloro-3-fluorophenylamino)methyl]phenyl}butanamide; N-{4-[(4-fluoro-phenylamino)methyl]-2-methylphenyl}butanamide; N-{4-[(3-fluorophenylamino)methyl]-2-methylphenyl}butanamide; N-{4-[(4-chlorophenylamino)methyl]-2-methylphenyl}butanamide;N-{4-[(3,4-dichlorophenylamino)methyl]-2-methylphenyl}butanamide; N-{4-[(4-chloro-3-fluorophenylamino)methyl]-2-methylphenyl}butanamide; N-{2-chloro-4-[(4-trifluoromethylphenylamino)methyl]phenyl}butanamide; N-{2-chloro-4-[(4-fluorophenylamino)methyl]phenyl}butanamide; N-{2-chloro-4-[(3-fluorophenylamino)methyl]phenyl}butanamide; N-{2-chloro-4-[(4-chlorophenylamino)methyl]phenyl}butanamide; N-{2-chloro-4-[(3,4-dichlorophenylamino)methyl]phenyl}butanamide; N-{2-chloro-4-[(4-chloro-3-fluorophenylamino)methyl]phenyl}butanamide; N-{2-fluoro-4-[(3-fluorophenylamino)methyl]phenyl}butanamide; N-{4-[(4-chlorophenylamino)methyl]-2-fluorophenyl}butanamide; N-{2-fluoro-4-[(4-trifluoromethylphenylamino)methyl]phenyl}butanamide; N-{-4-[(3,4-dichlorophenylamino)methyl]-2-fluorophenyl}butanamide; N-{4-[(4-chloro-3-fluorophenylamino)methyl]-2-fluorophenyl}butanamide; and pharmaceutically acceptable salts thereof.

[0395] In another embodiment, the Kv7 channel activator is a compound according to Formula 11, wherein: U is O, S or C, s is O or 1; X is CO or SO2; Z is O, S or NR. , wherein R 4 Selected from the group consisting of: hydrogen, C 1-6-alk(ene / ynyl), C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(enyne) and hydroxy-C 3-8 -cycloalkyl(enyl); q is O or 1; R 1 and R 1 'Independently selected from the group consisting of: hydrogen, C \.6 -Alkyl (ene / ynyl), C3 -8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-Ci -6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(en / yn)yl and halo-C 3-8 -cycloalkyl (enyl) group; R is selected from the group consisting of hydrogen, halogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-Cι-6 -alk(ene / ynyl), Ar, Ar-C 1-6 -alk(ene / ynyl), Ar-C 3-8 -cycloalkyl (alkenyl), acyl, hydroxy-Cι -6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl (enyl) and cyano; provided that when R 2 is halogen or cyano, then s is 0; and when s is 1 and U is NR 2 ', then R 2 'Selected from the group consisting of: hydrogen, C 1-6 -alk(enyne) group, C -8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-Cι -6 -alk(ene / ynyl), Ar, Ar-C 1-6 -alk(ene / ynyl), Ar-C 3-8 -cycloalkyl (alkenyl), acyl, hydroxy-6-alk (alkenyl / ynyl), hydroxy-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(en / yn)yl and halo-C 3-8 -cycloalkyl(enyl) group; or R 2 and R 2 ' together form a 5-8 membered saturated or unsaturated ring optionally containing one additional heteroatom; R 3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-Cι -6 -alk(ene / ynyl), Ar, Ar-C 1-6 -alk(ene / ynyl), Ar-C 3-8 -cycloalkyl (alkenyl) group, hydroxy-Cι -6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl (alkenyl), halogenated-Cj.6-alk(ene / ynyl) and halogenated-C 3-8 -cycloalkyl(en)yl; and Y is selected from a group according to the following formula selected from the group consisting of:

[0396]

[0397] wherein: the line represents the bond connecting the group represented by Y to the nitrogen atom; W is O or S; a is 0, 1, 2, or 3; b is 0, 1, 2, 3, or 4; c is 0 or 1; d is 0, 1, 2, or 3; e is 0, 1, or 2; f is 0, 1, 2, 3, 4, or 5; g is 0, 1, 2, 3, or 4; h is 0, 1, 2, or 3; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(enyne) group, C 3-8 -cycloalkyl(enyl), Ar, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(enyne) group, Ar-Cι -6 -alk(ene / ynyl), acyl, C 1-6 -alkane (hydrocarbon / alkene / ynyl) oxy, halogen, halogenated-Cι -6 -Alkyl (ene / yne) group, -CO-NR 6 R 6 ', cyano, nitro, -NR 7 R 7 '、-SR 8 、-SO2R 8 and SO2OR 8 ; or two substituents together form a 5-8 membered saturated or unsaturated ring optionally containing one or two heteroatoms; R 6 and R 6 'Independently selected from the group consisting of: hydrogen, C \.6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group and Ar; R 7 and R 7 'Independently selected from the group consisting of: hydrogen, C \.6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, Ar and acyl; and R 8 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-Cι -6 -Alk(en / yn)yl, Ar and -NR 9 R 9 ; where R 9 and R 9 'Independently selected from the group consisting of: hydrogen, C6-alk(ene / yn)yl, C 3-8 -cycloalkyl(enyl) and C3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl); provided that; when R 5 It is SO2OR 8 When R 8 No—NR 9 R 9' ; and when R 5 It is SO2R 8 When R 8 is not a hydrogen atom; or a salt thereof; provided that the compound of formula I is not: 2-[[[4-(acetylamino)phenyl]methyl]amino]-5-chloro-N-(5-chloro-2-pyridyl)-benzamide; N-[4-[[(3,4,5-trimethoxyphenyl)amino]methyl]phenyl]-acetamide; N-[4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)amino]methyl]phenyl]-acetamide; N-[4-[[[3-(1H-imidazol-1-ylmethyl)phenyl]amino]methyl]phenyl]-acetamide ; N-[4-[[[2-(1H-imidazol-1-ylmethyl)phenyl]amino]methyl]phenyl]-acetamide; N-[4-[[[4-(1H-imidazol-1-ylmethyl)phenyl]amino]methyl]phenyl]-acetamide; N-[4-[[(4-amino-3,5-dichlorophenyl)amino]methyl]phenyl]-acetamide; N-[4-[[(2,4-diamino-6-quinazolinyl)amino]methyl]phenyl]-acetamide; or N-[4-[[(2,4-diamino-6-quinazolinyl)amino]methyl]phenyl]-acetamide.

[0398] In further embodiments, the Kv7 channel activator is a compound according to Formula 11, wherein: wherein U is O, S or NR 2 , s is O or 1; X is CO or SO2; Z is O, S or NR; wherein R is selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), C3-s-cycloUc (alkenyl) -Cι -6 -alk(ene / ynyl) group, hydroxyl-Cι -6 -alk(en / yn)yl and hydroxy-C 3-8 -cycloalkyl (ene) group; q is 0 or 1; 1 1 'R and R are independently selected from the group consisting of: hydrogen, Cι_6-alkane (ene / alkynyl), C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1.6 -alk(ene / ynyl), acyl, hydroxy-Ci -6 -alk(ene / ynyl), hydroxy-C 3-8-cycloalkyl (alkenyl), halogenated -C1_.6-alk(ene / alkynyl) and halogenated -C 3.8 -cycloalkyl (enyl) group; R is selected from the group consisting of hydrogen, halogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-Cι -6 -alk(enyne) group, Ar, Ar-Ci -6 -alk(ene / ynyl), Ar-C 3-8 -cycloalkyl (alkenyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl) group, halo-Cι -6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl (enyl) and cyano; provided that when R 2 is halogen or cyano, then s is 0; and when s is 1 and U is NR 2 When R 2' Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C -8 -cycloalkyl(enyl) group, C .8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar-C 1-6 -alk(ene / ynyl), Ar-C 3.8 -cycloalkyl (alkenyl), acyl, hydroxy-C^6-alk(ene / ynyl), hydroxy-C^6-alk(ene / ynyl), 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(en / yn)yl and halo-C 3-8 -cycloalkyl(en)yl; or R and R together form a 5-8 membered saturated or unsaturated ring optionally containing one additional heteroatom; R 3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(enyne) group, Ar, Ar-C 1-6 -alk(ene / ynyl), Ar-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), halo-Ci-6-alk (enynyl) and halo-Ci-6-alk (enynyl) 3- S-cycloalkyl (en) group; and Y is selected from the group according to the following formula, the formula is selected from the group consisting of:

[0399]

[0400] wherein the line represents the bond connecting the group represented by Y to the nitrogen atom; W is O or S; a is 0, 1, 2, or 3; h is 0, 1, 2, 3, or 4; c is 0 or 1; d is 0, 1, 2, or 3; e is 0, 1, or 2; f is 0, 1, 2, 3, 4, or 5; is 0, 1, 2, 3, or 4; h is 0, 1, 2, or 3; and each R 5 Independently selected from the group consisting of: C -6 -alk(ene / ynyl) group, C 3.8 -cycloalkyl (alkenyl), Ar, Cs-s-cycloall^ei^yl-Ci-e-all^en / ^yl, Ar-Cι -6 -alk(ene / ynyl), acyl, C 1-6 -alkane (hydrocarbon / alkene / ynyl) oxy, halogen, halogenated-C 1-6 -Alkyl (ene / yne) group, -CO-NR 6 R 6' , cyano, nitro, -NR 7 R 7 '、-SR 8 、-SO2R 8 and SO2OR 8 ; or two substituents together form a 5-8 membered saturated or unsaturated ring optionally containing one or two heteroatoms; R 6 and R 6 independently selected from the group consisting of: hydrogen, C \.6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group and Ar; R 7 and R 7 'Independently selected from the group consisting of: hydrogen, Cj.6-alk(ene / ynyl), C 3-8 -cycloalkyl (enyl) group, Cs-s-cycloall^en l--e-all^en / yn l, Ar and acyl; and R 8 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -Alk(en / yn)yl, Ar and -NR 9 R 9 ; where R 9 and R 9 'Independently selected from the group consisting of: hydrogen, Q.6-alk(ene / yn)yl, C 3-8 -cycloalkyl(enyl) and C3-8 -cycloalkyl(enyl)-Cι -6 -alk(enyne) group; provided that; when R 5 It is SO2OR 8 When R 8 No-NR 9 R 9 '; and when R 5 It is SO2R 8 When R s other than a hydrogen atom; or a salt thereof, to increase ion flux in a potassium channel in a mammal (eg, a human).

[0401] Formula 12

[0402] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 12. Such compounds are described in the following: International Publication No. WO2009015667A1 published on February 5, 2009 and corresponding to International Application No. PCT / DK2008 / 050191 filed on July 31, 2008; International Publication No. WO2004096767A published on November 11, 2004 and corresponding to International Application No. PCT / DK2004 / 000283 filed on April 23, 2004; No. 1, published on November 23, 2006, corresponding to U.S. application Ser. No. 10 / 551,738, filed on April 23, 2003; and U.S. application Ser. No. 20100256145 A1, published on October 7, 2010, corresponding to U.S. application Ser. No. 12 / 671,505, filed on July 31, 2008; each of which is incorporated herein by reference in its entirety. In the event of any conflict in the context of Formula 12, these references are incorporated herein by reference for all purposes.

[0403] In one embodiment, the Kv7 channel activator is a compound according to Formula 12:

[0404]

[0405] Wherein, the dotted line represents an optional bond; R 1 and R 1' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8-cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 1 and R 1' Together with the carbon atom to which it is attached, it forms a 3-8 membered saturated or unsaturated ring optionally containing 1 or 2 heteroatoms; s is 0 or 1; U is O, NR 11 、S、SO2、SO2NR 11 , CO—O or CO—NR 11 ; Among them: R 11 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 2 and R 2' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; R 2 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C1-6 -alk(ene / ynyl), cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, -NO2, NR 10 R 10'—C 1-6 Alkyl (ene / alkyne) group, NR 10 R 10' —C 3-8 -cycloalkyl (alkenyl) and NR 10 R 10' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein R 10 and R 10' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-Cl—6-alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, or R 10 and R 10' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that: when R 2 is NO2, halogen or cyano, then s is 0; and when R 2 、R 2 is a hydrogen atom or an acyl group and s is 1, then U is NR 11 , O or S; wherein the group—(U) s —R 2 attached to position 4 or 6 of indole or indoline; q is 0 or 1; Z is O or S; X is CO or SO2; provided that when q is 0, then X is SO2; R3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), heterocycloalkyl (alkenyl), C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, Ar, Ar-C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar-heterocycloalkyl (alkenyl), Ar-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), Ar—C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 3-8 -cycloalkyl(enyl) group, C 1-6 -alk(ene / ynyl)oxy-heterocycloalk(ene)yl, Ar-oxy-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-heterocycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 1-6-Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl (alkenyl), halogenated heterocycloalkyl (alkenyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 1-6 -Alk(ene / ynyl)-Ar, halo-C 3-8 -cycloalkyl (alkenyl)-Ar, halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alk(ene / ynyl)-Ar, halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (enyl)-Ar, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-heterocycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), cyano-C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, acyl -C 1-6 -alk(ene / ynyl), acyl-C 3-8 -cycloalkyl (enyl), acyl-heterocycloalkyl (enyl), acyl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl) group, acyl-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, NR 12 R 12' , optionally substituted NR 12 R 12' —C 1-6 -alk(en / yn)yl, optionally substituted NR 12 R 12' —C 3-8 -cycloalkyl(en)yl and optionally substituted NR 12 R 12' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein: R 12 and R12' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 12 and R 12' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that: when R 3 It is NR 12 R 12' When , q is 0; and Y represents a formula from the following group:

[0406]

[0407] wherein: the line represents a bond connecting the group represented by Y to a carbon atom; W is O or S; T is N, NE or O; L is N, C or CH; a is 0, 1, 2 or 3; b is 0, 1, 2, 3 or 4; c is 0 or 1; d is 0, 1, 2 or 3; e is 0, 1 or 2; f is 0, 1, 2, 3, 4 or 5; g is 0, 1, 2, 3 or 4; h is 0, 1, 2 or 3; j is 0, 1, 2 or 3; provided that when T is a nitrogen atom, then j is 0, 1, 2 or 3; and when T is NH or an oxygen atom, then j is 0, 1 or 2; k is 0, 1, 2, 3 or 4; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar-thio, Ar-oxy, acyl, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, -CO-NR 6 R 6' , cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), -NR 7 R 7' 、—S—R 8 and—SO2R 8 ; or two adjacent R 5 The substituents together with the aromatic group to which they are attached form a 4-8 membered ring optionally containing one or two heteroatoms; wherein: R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group and Ar; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, Ar and acyl; and R 8 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar and -NR 9 R 9' ; where R 9 and R9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl); provided that when R 8 Yes—NR 9 R 9' When R 5 Not—S—R 8 or a pharmaceutically acceptable salt thereof. Provided that the compound of Formula I is not: N-[1-(phenylmethyl)-1H-indol-5-yl]-methanesulfonamide; N-[1-[(4-fluorophenyl)methyl]-1H-indol-5-yl]-methanesulfonamide; N-[2,3-dihydro-1-(phenylmethyl)-1H-indol-5-yl]-methanesulfonamide; N-[1-(phenylmethyl)-1H-indol-5-yl]-N'-4-quinolinyl-urea; N-[1-(phenylmethyl)-1H-indol-5-yl]-N'-4-quinolinyl-urea; or 1-(1-benzyl-5-indolinyl)-3-phenyl-urea; or a salt thereof.

[0408] In another embodiment, R 1 or R 1' At least one of them is a hydrogen atom.

[0409] In another embodiment, R 1 and R 1' It's a hydrogen atom.

[0410] In further embodiments, s is 0.

[0411] In another embodiment, s is 1.

[0412] In another embodiment, R 2 It's a hydrogen atom.

[0413] In another embodiment, R 2 It is NO2 or a halogen atom.

[0414] In another embodiment, U is NR 11 .

[0415] In another embodiment, R 11 It's a hydrogen atom.

[0416] In further embodiments, X is CO.

[0417] In further embodiments, X is SO2.

[0418] In another embodiment, q is 0.

[0419] In another embodiment, q is 1.

[0420] In further embodiments, Z is an oxygen atom.

[0421] In another embodiment, R 3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar-oxy-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(en / yn)yl and -NR 12 R 12' ; The condition is that when R 3 Time NR 12 R 12' When , q is 0.

[0422] In another embodiment, R 3 It is NR 12 R 12' , q is 0, and R 12 and R 12' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl), Ar and Ar-C 1-6 -alk(en / yn)yl; or R 12 and R 12' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring which optionally contains 1, 2 or 3 further heteroatoms.

[0423] In another embodiment, each R 5 Independently selected from the group consisting of: C 1-6 -alk(en / yn)yl, Ar, Ar-thio, Ar-oxy, halogen and halo-C 1-6 -alk(en / yn) group, or two adjacent R 5 Together with the aromatic group to which it is attached, it forms a 4-8 membered ring optionally containing one or two heteroatoms.

[0424] In further embodiments, the Kv7 channel activator is selected from the group consisting of: N-[4-chloro-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[4-chloro-1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; [1-(4-fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-carbamic acid propyl ester; N-[1-(4-fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-C-phenyl-methanesulfonamide; 4-fluoro-N-[1-(4-fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-phenylmethanesulfonamide N-[1-(4-Fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[1-(4-Fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-2-thiophen-2-ylacetamide; N-[1-(4-Fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; 3-[1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-1,1-diisopropylurea; morpholine-4-carboxylic acid [1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-amide; pyrrolidine-1-carboxylic acid [1-(5-chlorothiophen- [1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-carbamic acid 2-benzyloxyethyl ester; 3-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1-propyl urea; [1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-carbamic acid tert-butyl ester; N-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-C-phenyl-methanesulfonamide; [1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-C-phenyl-methanesulfonamide; [1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butane-1-sulfonic acid [1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1-propyl urea]; [1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-carbamic acid tert-butyl ester; N-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-4-fluorobenzamide; N-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropanamide; N-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2-phenoxyacetamide; N-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[1-(5-Chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butanamide;Cyclopentanecarboxylic acid [1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-amide; N-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2-thien-2-ylacetamide; N-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-isonicotinamide; N-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-4-dimethylaminobenzamide; N-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; N-[1-( 1-tert-Butyl-3-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-urea; 1-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-ethylurea; 1-Benzyl-3-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-urea; 1-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-phenylethylurea; 1-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-phenylethylurea 1-[1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-thien-3-ylurea; [1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-thien-3-ylurea; [1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propyl carbamate; 2,2-dimethyl-N-[6-nitro-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-propionamide; N-[1-(5-chlorothien-2-ylmethyl)-6-nitro-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropionamide; 2-(4-fluorophenyl)-N-[6-nitro-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-propionamide N-[1-(5-chlorothien-2-ylmethyl)-6-nitro-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; N-[1-(5-chlorothien-2-ylmethyl)-6-nitro-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[6-amino-1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[6-amino-1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[6-amino-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropanamide;N-[6-amino-1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropanamide; N-[6-amino-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; N-[6-amino-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide, N-[6-amino-1-(4-fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[6-amino-1-(3-fluoro-4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]- 3,3-dimethylbutanamide; N-[1-(5-chlorothien-2-ylmethyl)-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[6-bromo-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[6-bromo-1-(5-chlorothien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[1-(4-chlorobenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; 3,3-dimethyl-N-[1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-butanamide; N-[1- (4-isopropylbenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[1-(3-fluoro-4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[1-(6-chlorobenzo[1,3]dioxolan-5-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide, N-[1-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutanamide; N-[1-(2-chloro-5-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]- 3,3-dimethylbutanamide; N-{1-[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-3,3-dimethylbutanamide; 3,3-dimethyl-N-[1-(6-p-tolyloxy-pyridin-3-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butanamide; N-{1-[6-(4-chlorophenylthio)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-3,3-dimethylbutanamide, N-{1-[6-(4-cyanophenoxy)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-3,3-dimethylbutanamide;3,3-Dimethyl-N-[1-(6-trifluoromethylpyridin-3-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; 3,3-Dimethyl-N-[1-(3-methyl-benzo[b]thien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; N-[1-(6-fluoro-4H-benzo[1,3]dioxin-8-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutyramide; 3,3-Dimethyl-N-[1-(6-phenoxypyridin-3-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; 3,3-Dimethyl-N-[1-(3-methyl-5-phenyl-isoxazole -4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide, N-(1-benzo[b]thien-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-3,3-dimethylbutyramide; N-{1-[1-(4-fluorophenyl)-5-methyl-1H-pyrazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-3,3-dimethylbutyramide; 3,3-dimethyl-N-[1-(5-methylthien-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; 3,3-dimethyl-N-[1-(4-pyrrol-1-yl-benzyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; N-[1-(4 2-(4-Fluorophenyl)-N-[1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; 2-(4-Fluorophenyl)-N-[1-(4-isopropylbenzyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; 2-(4-Fluorophenyl)-N-[1-(3-fluoro-4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; N-[1-(6-chlorobenzo[1,3]dioxolan-5-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide N-[1-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; N-[1-(2-chloro-5-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; N-{1-[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-2-(4-fluorophenyl)-acetamide; N-{1-[6-(4-cyanophenoxy)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-2-(4-fluorophenyl)-acetamide;2-(4-Fluorophenyl)-N-[1-(3-methyl-benzo[b]thiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; N-[1-(6-fluoro-4H-benzo[1,3]dioxin-8-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; 2-(4-Fluorophenyl)-N-[1-(6-phenoxypyridin-3-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; N-(1-Benzo[b]thiophen-2-ylmethyl-2,3-dihydro-1H-indol-8-ylmethyl)-2,3-dihydro-1H-indol-5-yl)-acetamide indol-5-yl)-2-(4-fluorophenyl)-acetamide; 2-(4-fluorophenyl)-N-{1-[1-(4-fluorophenyl)-5-methyl-1H-pyrazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-acetamide; 2-(4-fluorophenyl)-N-[1-(5-methylthiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; 2-(4-fluorophenyl)-N-[1-(4-pyrrol-1-yl-benzyl)-2,3-dihydro-1H-indol-5-yl]-acetamide; and pharmaceutically acceptable salts thereof.

[0425] Formula 13

[0426] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 13. Such compounds are described in the following: International Publication No. WO2009015667A1, published on February 5, 2009, corresponding to International Application No. PCT / DK2008 / 050191, filed on July 31, 2008; U.S. Publication No. US20100256145A1, published on October 7, 2010, corresponding to U.S. Application No. 12 / 671,505, filed on July 31, 2008; the entireties of which are incorporated herein by reference. In the event of any conflict in the context of Formula 13, these references are incorporated herein by reference for reference.

[0427] In one embodiment, the Kv7 channel activator is a compound according to Formula 13.

[0428]

[0429] wherein: q is 0 or 1; W is O or S; X is CO; Z is O; R1 is selected from the group consisting of: halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6-alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy; R2 is selected from the group consisting of: halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, optionally substituted phenyl and optionally substituted pyridyl; wherein phenyl and pyridyl are optionally substituted by one or more independently halogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) or C 3-8 -cycloalkyl(enyl)-C 1-6 -substituted by an alk(ene / yn) group; R3 is selected from the group consisting of: C 1-10 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl and Ar; and each of R4, R5, R6 and R7 is independently selected from the group consisting of hydrogen and Ar; as a free base or a salt thereof.

[0430] In further embodiments, the Kv7 channel activator is selected from the group consisting of: N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-2-(4-fluoro-phenyl)-acetamide; 2-cyclopentyl-N-(2-bromo-6-trifluoromethyl-4-morpholin-4-yl-phenyl)-acetamide; N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-3-cyclopentyl-propionamide; N-(2-chloro-6-cyano-4-morpholin-4-yl-phenyl)-3-cyclohexyl-propionamide; 2-cyclopentyl-N-(2,6-dimethyl-4-thiomorpholin-4-yl-phenyl)-acetamide; 2-cyclopentyl-N-[2,6-dimethyl-4-(2-phenyl-morpholin-4-yl)- )-phenyl]-acetamide; 2-cyclopentyl-N-[2,6-dimethyl-4-(2-phenyl-thiomorpholin-4-yl)-phenyl]-acetamide; 2-cyclopentyl-N-[2,6-dimethyl-4-(3-pyridin-3-yl-thiomorpholin-4-yl)-phenyl]-acetamide; 2-cyclopentyl-N-{2,6-dimethyl-4-[2-(4-trifluoromethyl-phenyl)-thiomorpholin-4-yl]-phenyl}-acetamide; N-{4-[2-(2-chloro-phenyl)-thiomorpholin-4-yl]-2,6-dimethyl-phenyl}-2-cyclopentyl-acetamide; 2-bicyclo[2.2.1]hept-2-yl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide ; 2-cyclohexyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; 3-(3,4-difluoro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-propionamide; 2-cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; (2,6-dimethyl-4-morpholin-4-yl-phenyl)-carbamic acid butyl ester; 2-(4-chloro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; 2,3-dihydro-benzofuran-2-carboxylic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 3-cyclohexyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-propionamide -phenyl)-propionamide; 3-cyclopentyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-propionamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-(4-fluoro-phenyl)-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-thiophen-2-yl-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-3,3-dimethyl-butyramide; hexanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 2-cycloheptyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; benzyl (2,6-dimethyl-4-morpholin-4-yl-phenyl)-carbamate;(2,6-Dimethyl-4-morpholin-4-yl-phenyl)-carbamic acid 2-chloro-benzyl ester; 3,5,5-trimethyl-hexanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; octanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; heptanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-phenyl-acetamide; 2-(3,4-dichloro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; 2-(4-allyloxy-3-chloro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; N-( 2,6-Dimethyl-4-morpholin-4-yl-phenyl)-2-(3-trifluoromethyl-phenyl)-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-naphth-2-yl-acetamide; 3-(3-chloro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-propionamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-(3,4-dimethyl-phenyl)-acetamide; 2-(3-bromo-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; 2-(3-chloro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide -4-yl-phenyl)-2-p-tolyl-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-m-tolyl-acetamide; 2-(3,4-difluoro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-2-(3-fluoro-phenyl)-acetamide; N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-3-cyclohexyl-propionamide; N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-2-(3-fluoro-phenyl)-acetamide; N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-propionamide; N-(2 -bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-butyramide; N-(2-chloro-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-2-(3-fluoro-phenyl)-acetamide; N-(2-chloro-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-2-cyclopentyl-acetamide; 2-cyclopentyl-N-{2,6-dimethyl-4-[2-(4-trifluoromethyl-phenyl)-morpholin-4-yl]-phenyl}-acetamide; N-{4-[2-(2-chloro-phenyl)-morpholin-4-yl]-2,6-dimethyl-phenyl}-2-cyclopentyl-acetamide; 2-cyclopentyl-N-{4-[2-(4-fluoro-phenyl)-morpholin-4-yl]-2,6-dimethyl-phenyl}-acetamide;2-(2-Chloro-phenyl)-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; valeric acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 4-methyl-valeric acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 2-cyclopent-2-enyl-N-(2,6-dimethyl-4-morpholin-4-yl-phenyl)-acetamide; 5-methyl-hexanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 3-methyl-valeric acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; hex-5-enoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 3-ethyl-valeric acid (2, 6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 2-cyclopentyl-N-(4-morpholin-4-yl-2-pyridin-3-yl-6-trifluoromethyl-phenyl)-acetamide; 2-cyclopentyl-N-(5-morpholin-4-yl-3-trifluoromethyl-biphenyl-2-yl)-acetamide; 2-cyclopentyl-N-(4'-fluoro-5-morpholin-4-yl-3-trifluoromethyl-biphenyl-2-yl)-acetamide; 2-cyclopentyl-N-(4'-methyl-5-morpholin-4-yl-3-trifluoromethyl-biphenyl-2-yl)-acetamide, 2-cyclopentyl-N-(3'-methyl-5-morpholin-4-yl-3-trifluoromethyl-biphenyl-2-yl)-acetamide; 2-cyclopentyl-N-(3',4 '-Difluoro-5-morpholin-4-yl-3-trifluoromethyl-biphenyl-2-yl)-acetamide; 2-(4-Fluoro-phenyl)-N-(4-morpholin-4-yl-2-pyridin-3-yl-6-trifluoromethyl-phenyl)-acetamide; 2-Cyclopentyl-N-(2,6-diethyl-4-morpholin-4-yl-phenyl)-acetamide; 2-Cyclopentyl-N-(2,6-diisopropyl-4-morpholin-4-yl-phenyl)-acetamide; 2-Cyclopentyl-N-(2,6-difluoro-4-morpholin-4-yl-phenyl)-acetamide; Hexanoic acid (2,6-difluoro-4-morpholin-4-yl-phenyl)-amide; N-(2,6-difluoro-4-morpholin-4-yl-phenyl)-3,3-dimethyl-butyryl Amine; N-(2,6-difluoro-4-morpholin-4-yl-phenyl)-2-(3-fluoro-phenyl)-acetamide; 2-cyclopent-2-enyl-N-(2,6-difluoro-4-morpholin-4-yl-phenyl)-acetamide; 2-bicyclo[2.2.1]hept-2-yl-N-(2,6-difluoro-4-morpholin-4-yl-phenyl)-acetamide; 2-bicyclo[2.2.1]hept-2-yl-N-(2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-acetamide; 5-methyl-pentanoic acid (2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-amide; 5-methyl-hexanoic acid (2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-amide;2-Cyclopent-2-enyl-N-(2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-acetamide; 2-Cyclopentyl-N-(2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-acetamide; Hexanoic acid (2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-amide; 3,3-Dimethyl-N-(2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-butyramide; 2-(3,4-difluoro -phenyl)-N-(2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-acetamide; hexanoic acid (2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-amide; 2-cyclopentyl-N-(2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-acetamide; N-(2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-3,3-dimethyl-butyramide; 2-(3,4-difluoro-phenyl)-N-(2 -methoxy-6-methyl-4-morpholin-4-yl-phenyl)-acetamide; 2-cyclopent-2-enyl-N-(2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-acetamide; 2-(3-fluoro-phenyl)-N-(2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-acetamide; 2-bicyclo[2.2.1]hept-2-yl-N-(2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-acetamide; 4- Methyl-pentanoic acid (2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-amide; 5-methyl-hexanoic acid (2-methoxy-6-methyl-4-morpholin-4-yl-phenyl)-amide; N-(2-chloro-6-methyl-4-morpholin-4-yl-phenyl)-2-(3-fluoro-phenyl)-acetamide; and N-(2-chloro-6-methyl-4-morpholin-4-yl-phenyl)-2-cyclopentyl-acetamide; as free base or pharmaceutically acceptable salts thereof.

[0431] Formula 14

[0432] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 14. Such compounds are described in: International Publication No. WO2009015667A1 published on February 5, 2008 and corresponding to International Application No. PCT / DK2008 / 050191 filed on July 31, 2008; International Publication No. WO200602962 published on March 23, 2006 and corresponding to International Application No. PCT / DK2005 / 000560 filed on September 2, 2005; No. 3A1; U.S. Patent No. 7,601,870, issued on October 13, 2009, corresponding to U.S. application No. 11 / 312,664, filed on December 20, 2005; U.S. Publication No. US20100256145A1, published on October 7, 2010, corresponding to U.S. application No. 12 / 671,505, filed on July 31, 2008; the disclosures of which are incorporated herein by reference in their entireties. In the event of any conflict in the context of Formula 14, these references are hereby incorporated by reference herein for all purposes.

[0433] In one embodiment, the Kv7 channel activator is a compound according to Formula 14:

[0434]

[0435] Wherein, Z is O or S; q is 0 or 1; R 1 and R 2 Each of which is independently selected from the group consisting of halogen, cyano, amino, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 3-8 -heterocycloalkyl (alkenyl), aryl, heteroaryl, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy and C 3-8 -heterocycloalk(en)yloxy; R 3 Selected from the group consisting of: C 1-8 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, heteroaryl-C alk(en / yn)yl, heteroaryl-C 3-8 -cycloalkyl(enyl) group, heteroaryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl) group, amino-C 1-6 -Alkyl (ene / ynyl) group, amino-C 3-8 -cycloalkyl (enyl) group, amino-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; and R 4 Selected from the group consisting of: halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 3-8 -heterocycloalkyl (alkenyl), aryl, heteroaryl, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -heterocycloalkyl(enyl) group, halogenated-C 1-6-alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(en / yn)yl-C 3-8 -heterocycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 5 R 6 and R 7 NH—C 1-6 -alk(en / yn)yl; wherein: R 5 and R 6 are independently selected from the group consisting of: hydrogen, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, heteroaryl-C 1-6 -alk(en / yn)yl, heteroaryl-C 3-8 -cycloalkyl(enyl) and heteroaryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, provided that R 5 and R 6 are not both hydrogen; and R 7 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), aryl, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl(en)yl and heteroaryl; or a pharmaceutically acceptable salt thereof.

[0436] In further embodiments, the Kv7 channel activator is selected from the group consisting of hexanoic acid (4-bromo-2,6-dimethyl-phenyl)-amide; N-(4-bromo-2,6-dimethyl-phenyl)-2-(4-fluoro-phenyl)-acetamide; N-(2-bromo-4,6-dimethyl-phenyl)-2-(4-fluoro-phenyl)-acetamide; N-(2-bromo-4,6-dimethyl-phenyl)-3,3-dimethyl-butyramide; N-(2-bromo-4,6-dimethyl-phenyl)-2-cyclopentyl-acetamide; N-(2-bromo-4,6-dimethyl-phenyl)-3,3-dimethyl-butyramide; N-(2-bromo-4,6-dichloro-phenyl)-2-(4-fluoro-phenyl)-acetamide; N-(2-Bromo-4,6-dichloro-phenyl)-2-cyclopentyl-acetamide; heptanoic acid (4-bromo-2,6-dimethyl-phenyl)-amide; cyclohexanecarboxylic acid (4-bromo-2,6-dimethyl-phenyl)-amide; N-(4-bromo-2,6-dimethyl-phenyl)-2-thiophen-2-yl-acetamide; 2-phenyl-cyclopropanecarboxylic acid (4-bromo-2,6-dimethyl-phenyl)-amide; N-(4-bromo-2,6-dimethyl-phenyl)-2-(4-chloro-phenyl)-acetamide; valeric acid (4-bromo-2,6-dimethyl-phenyl)-amide; octanoic acid (4-bromo-2,6-dimethyl-phenyl)-amide; N-(4-bromo-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide Amide; 2-bicyclo[2.2.1]hept-2-yl-N-(2,4-difluoro-6-morpholin-4-yl-phenyl)-acetamide; (S)-2-amino-N-{2,6-dimethyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-3-methyl-butyramide; (S)-2-amino-4-methyl-pentanoic acid {2,6-dimethyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-amide; (4-bromo-2,6-dimethyl-phenyl)-carbamic acid ethyl ester; (4-bromo-2,6-dimethyl-phenyl)-carbamic acid propyl ester; N-(2-amino-4-bromo-6-methyl-phenyl)-3,3-dimethyl-butyramide; 2-cyclo Pentyl-N-{2,6-dimethyl-4-[2-(4-trifluoromethyl-phenyl)-pyrrolidin-1-yl]-phenyl}-acetamide; N-(4-azepan-1-yl-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide; 2-cyclopentyl-N-(2,6-dimethyl-4-pyrrol-1-yl-phenyl)-acetamide; N-(3'-amino-3,5-dimethyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; N-(4'-dimethylamino-3,5-dimethyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; N-(2,4-dimethyl-6-quinolin-3-yl-phenyl)-2-(4-fluoro-phenyl)-acetamide;2-(4-Fluoro-phenyl)-N-(4'-hydroxy-3'-methoxy-3,5-dimethyl-biphenyl-2-yl)-acetamide; 2-(4-Fluoro-phenyl)-N-(3'-hydroxy-3,5-dimethyl-biphenyl-2-yl)-acetamide; 2-(4-Fluoro-phenyl)-N-(2'-methanesulfonylamino-3,5-dimethyl-biphenyl-2-yl)-acetamide; N-(4'-isopropyl-3,5-dimethyl-biphenyl-2-yl)-3,3-dimethyl-butyramide; 2-cyclopentyl-N-(3,5-dimethyl-biphenyl-2-yl)-acetamide; N-(4'-Fluoro-3,5-dimethyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; N-(3 ,5-dimethyl-3',5'-bis-trifluoromethyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; N-(3'-acetylamino-3,5-dimethyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; 2-(4-fluoro-phenyl)-N-(2'-methoxy-3,5-dimethyl-biphenyl-2-yl)-acetamide; N-(3,5-dimethyl-4'-vinyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; N-(3'-cyano-3,5-dimethyl-biphenyl-2-yl)-2-(4-fluoro-phenyl)-acetamide; N-(3,5-dimethyl-3'-trifluoromethoxy-biphenyl-2-yl)-2-(4-fluoro- phenyl)-acetamide; N-[2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-4,6-dimethyl-phenyl]-2-(4-fluoro-phenyl)-acetamide; N-[2,4-dimethyl-6-(2,2,5-trimethyl-2,3-dihydro-benzofuran-7-yl)-phenyl]-2-(4-fluoro-phenyl)-acetamide; N-[2,6-dimethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-acetamide; N-{2,6-dimethyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-acetamide; {4-[(5-chloro-thiophen-2-ylmethyl)-amino]-2,6-dimethyl-phenyl}-carbamic acid propyl ester; [ 4-(4-Fluoro-benzylamino)-2,6-dimethyl-phenyl]-carbamic acid propyl ester; [2,6-dimethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-carbamic acid propyl ester; [4-(3-Fluoro-4-trifluoromethyl-benzylamino)-2,6-dimethyl-phenyl]-carbamic acid propyl ester; {2,6-dimethyl-4-[(4-methyl-2-phenyl-pyrimidin-5-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; {2,6-dimethyl-4-[(6-p-tolyloxy-pyridin-3-ylmethyl)-amino]-phenyl}-carbamic acid propyl ester; {4-[(6-methoxy-pyridin-3-ylmethyl)-amino]-2,6-dimethyl-phenyl}-carbamic acid propyl ester;{4-[(3-Fluoro-4-trifluoromethyl-benzyl)-methyl-amino]-2,6-dimethyl-phenyl}-carbamic acid propyl ester; 2-cyclopentyl-N-[2,6-dimethyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-acetamide 2-cyclopentyl-N-{2,6-dimethyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-acetamide; 2-cyclopentyl-N-{2,6-dimethyl-4-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-phenyl}-acetamide; N-{2,6-dimethyl-4-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-phenyl}-3,3-dimethyl-butyramide; N-{2-bromo-4-[(5-chloro- -thiophen-2-ylmethyl)-amino]-6-trifluoromethyl-phenyl}-3-cyclohexyl-propionamide; {4-[(3-fluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid ethyl ester; {2,6-dimethyl-4-[(4-trifluoromethyl-phenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; 2-cyclopentyl-N-{4-[(3-fluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-acetamide; N-{4-[(3-chloro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-2-cyclopentyl-acetamide; 2-cyclopentyl-N-{4-[(3-methoxy-phenylamino)-methyl]-2,6-dimethyl-phenyl}-acetamide; N-{ 4-[(4-Chloro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-2-cyclopentyl-acetamide; 2-cyclopentyl-N-{4-[(3,4-difluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-acetamide; 2-cyclopentyl-N-{2,6-dimethyl-4-[(4-trifluoromethyl-phenylamino)-methyl]-phenyl}-acetamide; 2-cyclopentyl-N-[2,6-dimethyl-4-[(p-tolylamino-methyl)-phenyl]-acetamide; 2-cyclopentyl-N-{2,6-dimethyl-4-[(3-trifluoromethyl-phenylamino)-methyl]-phenyl}-acetamide; 2-cyclopentyl-N-{-4-[(3,5-difluoro-phenylamino)-methyl]- 2,6-Dimethyl-phenyl}-acetamide; {4-[(4-Fluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid propyl ester; {4-[(4-Chloro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid propyl ester; {2,6-dimethyl-4-[(4-trifluoromethyl-phenylamino)-methyl]-phenyl}-carbamic acid propyl ester; {4-[(3,5-difluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid propyl ester; {4-[(3-Fluoro-phenylamino)-methyl]-2,6-dimethyl-phenyl}-carbamic acid propyl ester; N-(4-Bromo-2-methyl-6-morpholin-4-yl-phenyl)-3,3-dimethyl-butyramide;{4-[(4-methoxyphenylamino)-methyl]-2,6-dimethylphenyl}-carbamic acid propyl ester; (R)-2-amino-4-methylpentanoic acid [2,6-dimethyl-4-(4-trifluoromethylbenzylamino)-phenyl]-amide; pentanoic acid (4-[(4-chlorophenylamino)-methyl]-2,6-dimethylphenyl)-amide; 2-(4-chlorophenyl)-N-[4-(4-chlorophenylamino)-methyl] -2,6-dimethylphenyl)-acetamide; {2,6-dimethyl-4-[(4-trifluoromethylphenylamino)-methyl]-phenyl}-carbamic acid 2-methoxyethyl ester; N-{4-[(5-chloro-pyridin-2-ylamino)-methyl]-2,6-dimethylphenyl}-2-cyclopentylacetamide; 2-cyclopentyl-N-{4-[(2,6-dichloro-pyridin-4-ylamino)-methyl]-2,6-dimethyl N-{2-chloro-6-methyl-4-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-phenyl}-2-(3-fluoro-phenyl)-acetamide; N-[2-chloro-6-trifluoromethyl-4-(4-trifluoromethylbenzylamino)-phenyl]-2-cyclopentylacetamide; [2-amino-6-methyl-4-(4-trifluoromethylbenzylamino)-phenyl]-carbamic acid ethyl ester; 3,3 -dimethyl-N-{2-methyl-6-morpholin-4-yl-4-(4-trifluoromethylbenzylamino)-phenyl}-butyramide; 2-cyclopentyl-N-{2,6-dichloro-4-[(4-fluoro-phenylamino)-methyl]-phenyl}-acetamide; 2-cyclopentyl-N-{2,6-dichloro-4-[(5-trifluoromethylpyridin-2-ylamino)-methyl]-phenyl}-acetamide; and pharmaceutically acceptable salts thereof. ;

[0437] In another embodiment, Z is O or S; q is 0; R 1 and R 2 Each independently selected from the group consisting of: halogen, cyano, amino, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), aryl, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy; R 3 Selected from the group consisting of: C1-8 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl) group, amino-C 1-6 -Alkyl (ene / ynyl) group, amino-C 3-8 -cycloalkyl(enyl) group, amino-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; and R 4 Selected from the group consisting of: halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 5 R 6 and R 7 NH—C 1-6 -alk(en / yn)yl; wherein: R 5 and R 6 are each independently selected from the group consisting of: hydrogen, aryl-C 1-6 -alk(en / yn)yl, aryl-C3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 Alkyl (ene / ynyl), provided that R 5 and R 6 cannot all be hydrogen; and R 7 Selected from the group consisting of: C 1-6 -alk(en / yn)yl; C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), aryl, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -Alk(en / yn)yl and aryl-C 3-8 -cycloalkyl(en)yl; proviso that the compound of formula I is not N-(4-bromo-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide; or a pharmaceutically acceptable salt thereof.

[0438] In another embodiment, R 1 and R 2 Each independently selected from the group consisting of: halogen, amino, C 1-6 -alk(en / yn)yl, aryl and halo-C 1-6 -alk(en / yn)yl.

[0439] In another embodiment, R 3 Selected from the group consisting of: C 1-8 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl(enyl) and amino-C 1-6 -alk(en / yn)yl.

[0440] In another embodiment, R 4 Selected from the group consisting of: halogen, C 1-6 -Alkyl (ene / yne) group, NR 5 R 6 and R7 NH—C 1-6 -alk(en / yn)yl, wherein R 5 、R 6 and R 7 As defined previously.

[0441] In another embodiment, R 4 It is NR 5 R 6 , where R 5 and R 6 are each independently selected from the group consisting of: hydrogen, aryl-C 1-6 -alk(en / yn) groups and C 1-6 -alk(en / yn)yl, provided that R 5 and R 6 It can't be all hydrogen.

[0442] In another embodiment, R 4 It is R 7 NH—C 1-6 -alk(en / yn)yl, wherein R 7 It is an aryl group.

[0443] In further embodiments, any aryl group is optionally substituted with one or more substituents independently selected from the group consisting of amino, halogen, cyano, C 1-6 -alk(ene / ynyl), halo-C 1-6 -Alkyl (ene / ynyl), hydroxyl, C 1-6 -alk(en / yn)yloxy, halo-C 1-6 -alk(en / yn)yloxy, di-(C 1-6 -alk(en / yn)yl)amino, C 1-6 -alk(ene / ynyl)-CO—NH— and C 1-6 -alk(ene / ynyl)-sulfonamide; or two adjacent substituents may form together with the aryl group to which they are attached a group which is optionally substituted by one or more C 1-6 - 4-8 membered ring substituted with alk(en / yn) group.

[0444] In further embodiments, the Kv7 channel activator is a compound according to Formula 14, wherein: Z is O or S; q is 0; R 1 and R 2 Each independently selected from the group consisting of: halogen, cyano, amino, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), aryl, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8-cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy; R 3 Selected from the group consisting of: C 1-8 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / ynyl) group, amino-C 1-6 -Alkyl (ene / ynyl) group, amino-C 3-8 -cycloalkyl(enyl) group, amino-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; and R 4 Selected from the group consisting of: halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8-cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 5 R 6 and R 7 NH—C 1-6 -alk(en / yn)yl; wherein: R 5 and R 6 are each independently selected from the group consisting of: hydrogen, aryl-C 1-6 -alk(en / yn)yl, aryl-C 3-8 -cycloalkyl (alkenyl) group, aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, provided that R 5 and R 6 cannot all be hydrogen; and R 7 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), aryl, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, aryl-C 1-6 -Alk(en / yn)yl and aryl-C 3-8 -cycloalkyl(en)yl; proviso that the compound of formula I is not N-(4-bromo-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier or diluent.

[0445] Formula 15

[0446] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 15. Such compounds are described in: International Publication No. WO2009015667A1 published on February 5, 2009 and corresponding to International Application No. PCT / DK2008 / 050191 filed on July 31, 2008; International Publication No. WO200609214 published on September 8, 2006 and corresponding to International Application No. PCT / DK2006 / 000123 filed on March 2, 2006; No. 3A1; U.S. Patent No. 7,812,020, issued on October 12, 2010, corresponding to U.S. Application No. 11 / 817,340, filed on March 2, 2006; U.S. Publication No. US20100256145A1, published on October 7, 2010, corresponding to U.S. Application No. 12 / 671,505, filed on July 31, 2008; the disclosures of which are incorporated herein by reference in their entireties. In the event of any conflict in the context of Formula 15, these references are hereby incorporated by reference herein for all purposes.

[0447] In one embodiment, the Kv7 channel activator is a compound according to Formula 15:

[0448]

[0449] Where q is 0 or 1; R 1 and R 2 Each of which is independently selected from the group consisting of halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy; and R 3 Selected from the group consisting of: C 1-8 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, optionally substituted aryl-C 1-6-alk(en / yn)yl, optionally substituted Aryl-C 3-8 -cycloalkyl(enyl), optionally substituted Aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(ene / ynyl) group, C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, heteroaryl-C 1-6 -alk(en / yn)yl, heteroaryl-C 3-8 -cycloalkyl(enyl) group, heteroaryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 4 R 5 —C 1-6 -Alkyl (ene / yne) group, NR 4 R 5 —C 3-8 -cycloalkyl (alkenyl), NR 4 R 5 —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein R 4 and R 5 Each of which is independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; as a free base or a pharmaceutically acceptable salt thereof.

[0450] In further embodiments, the Kv7 channel activator is selected from the group consisting of: (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)carbamic acid benzyl ester; (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-carbamic acid 2-chloro-benzyl ester; 2-(4-chloro-phenyl)-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; 2-phenyl-cyclopropanecarboxylic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-thiophen-2-yl-acetamide; 3-cyclohexyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)- phenyl)-propionamide; (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-carbamic acid isobutyl ester; 3-(3-chloro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-propionamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3,5-dimethyl-phenyl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3-p-tolyl-propionamide; 2-(3-chloro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; 2-(3,4-dichloro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)- -3-yl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-thiophen-3-yl-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-p-tolyl-acetamide; 2-(3-bromo-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3-trifluoromethyl-phenyl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-phenyl-acetamide; 3,5,5-trimethyl-hexanoic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin- 3-yl)-amide; octanoic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-naphth-2-yl-acetamide; heptanoic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3,4-dimethyl-phenyl)-acetamide; 2-cyclohex-1-enyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(4-methoxy-3-methyl-phenyl)-acetamide;N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(4-methoxy-phenyl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3-(4-methoxy-phenyl)-propionamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-m-tolyl-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(4-fluoro-phenyl)-acetamide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-3,3 -dimethyl-butyramide; N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-2-(3-fluoro-phenyl)-acetamide; 2-bicyclo[2.2.1]hept-2-yl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; 2-(3,4-difluoro-phenyl)-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; 4-methyl-pentanoic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide; 2-cyclopent-2-enyl-N-(2,4-dimethyl- 6-morpholin-4-yl-pyridin-3-yl)-acetamide; 2-cyclohexyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; 5-methyl-hexanoic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide; 2-cyclopentyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-acetamide; 3-cyclopentyl-N-(2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-propionamide; hexanoic acid (2,4-dimethyl-6-morpholin-4-yl-pyridin-3-yl)-amide; N- (4-chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-2-cyclopentyl acetamide; N-(2-chloro-4-methoxy-6-morpholin-4-yl-pyridin-3-yl)-2-cyclopentyl acetamide; N-(2-chloro-4-methoxy-6-morpholin-4-yl-pyridin-3-yl)-3,3-dimethylbutanamide; N-(4-chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-3,3-dimethylbutanamide; N-(4-chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-propionamide; and pharmaceutically acceptable salts thereof.

[0451] In other embodiments, q is 0 or 1; R 1 and R 2 are each independently selected from the group consisting of: halogen, cyano, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy; and R 3 Selected from the group consisting of: C 1-8 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, optionally substituted aryl-C 1-6 -alk(en / yn)yl, optionally substituted aryl-C 3-8 -cycloalkyl(en)yl, optionally substituted aryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -heterocycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, heteroaryl-C 1-6 -alk(en / yn)yl, heteroaryl-C 3-8 -cycloalkyl(enyl) group, heteroaryl-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, NR 4 R 5 —C 1-6 -Alkyl (ene / yne) group, NR 4 R 5 —C 3-8 -cycloalkyl (alkenyl), NR 4 R 5 —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 3-8-cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, wherein: R 4 and R 5 Each independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl.

[0452] Formula 16

[0453] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 16. Such compounds are described in the following: International Publication No. WO2009015667A1, published on February 5, 2009, corresponding to International Application No. PCT / DK2008 / 050191, filed on July 31, 2008; and U.S. Publication No. US20100256145A1, published on October 7, 2010, corresponding to U.S. Application No. 12 / 671,505, filed on July 31, 2008; the entireties of which are incorporated herein by reference. In the event of any conflict in the context of Formula 16, these references are incorporated herein by reference.

[0454] In one embodiment, the Kv7 channel activator is a compound according to Formula 16:

[0455] Where: q is 0 or 1; R 1 and R 2 are independently selected from hydrogen and optionally substituted aryl-C 1-6 -alk(ene / ynyl) groups, provided that R 1 and R 2 Not all hydrogen; or R 1 and R 2 Together with the nitrogen to which it is attached, it forms a 5-7 membered ring optionally containing additional heteroatoms; R 2 and R 4 independently selected from hydrogen, halogen, cyano, amino, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl), halogenated-C 1-6-alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, halo-C 1-6 -alk(en / yn)yloxy, halo-C 3-8 -cycloalkyl(enyl)oxy and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, provided that R 3 and R 4 Not all hydrogen; and R 5 Selected from the group consisting of: C 1-10 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, optionally substituted aryl-C 1-6 -alk(en / yn)yl and optionally substituted aryl; as a free base or a pharmaceutically acceptable salt thereof.

[0456] In further embodiments, the Kv7 channel activator is selected from the group consisting of: N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-cyclopentyl acetamide; N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-3,3-dimethylbutanamide; N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-(4-fluorophenyl)-acetamide; hexanoic acid [4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-amide; N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-(3-chlorophenyl)-acetamide ; 2-cyclopentyl-N-(4,6-dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-acetamide; N-(4,6-dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-3,3-dimethylbutanamide; N-(4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-2-(4-fluorophenyl)-acetamide; 2-(3,4-difluorophenyl)-N-(4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-acetamide; N-(4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-2-(3-fluorophenyl)-acetamide; and hexanoic acid (4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-amide; as a free base or a pharmaceutically acceptable salt thereof.

[0457] Formula 17

[0458] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 17. Such compounds are described in International Publication No. WO2007065449A1, published on June 14, 2007, corresponding to International Application No. PCT / DK2006 / 050039 filed on September 7, 2006; which is incorporated herein by reference in its entirety. In the event of any conflict in the context of Formula 17, this reference is incorporated herein by reference.

[0459] In one embodiment, the Kv7 channel activator is a compound according to Formula 17:

[0460]

[0461] Where: q is 0 or 1; R 1 and R 2 are independently selected from hydrogen and optionally substituted aryl-C 1-6 -alk(ene / ynyl) groups, provided that R 1 and R 2 Not all hydrogen, or R 1 and R 2 Together with the nitrogen to which it is attached, it forms a 5-7 membered ring optionally containing additional heteroatoms; R 3 and R 4 independently selected from hydrogen, halogen, cyano, amino, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl) group, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, halo-C 1-6 -alk(en / yn)yloxy, halo-C 3-8 -cycloalkyl(enyl)oxy and halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, provided that R 3 and R 4 Not all hydrogen; R 5 Selected from the group consisting of: C 1-10 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, optionally substituted aryl-C 1-6- alk(en / yn)yl and optionally substituted aryl; as a free base or a salt thereof.

[0462] In another embodiment, q is 0.

[0463] In another embodiment, q is 1.

[0464] In another embodiment, R 1 and R 2 are independently selected from hydrogen and optionally substituted aryl-C 1-6 -alk(en / yn)yl, provided that R 1 and R 2 Not all hydrogen.

[0465] In another embodiment, R 1 and R 2 Together with the nitrogen to which it is attached, it forms a 5-7 membered ring optionally containing additional heteroatoms.

[0466] In further embodiments, the additional heteroatom is oxygen.

[0467] In further embodiments, the ring is a 6-membered ring.

[0468] In further embodiments, the ring is a morpholine ring.

[0469] In another embodiment, R 3 and R 4 Independently selected from amino and C 1-6 - alk(en / yn)yl, preferably methyl.

[0470] In another embodiment, R 5 Selected from the group consisting of: C 1-10 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, optionally substituted aryl-C 1-6 - alk(en / yn)yl and optionally substituted aryl.

[0471] In further embodiments, the Kv7 channel activator is selected from the group consisting of: N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-cyclopentyl acetamide, N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-3,3-dimethylbutanamide, N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-(4-fluorophenyl)-acetamide, hexanoic acid [4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-amide, N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-(3-chlorophenyl)- )-acetamide, 2-cyclopentyl-N-(4,6-dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-acetamide, N-(4,6-dimethyl-2-morpholin-4-yl-pyrimidin-5-yl)-3,3-dimethylbutanamide, N-(4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-2-(4-fluorophenyl)-acetamide, 2-(3,4-difluorophenyl)-N-(4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-acetamide, N-(4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-2-(3-fluorophenyl)-acetamide and hexanoic acid (4,6-dimethyl-2-morpholin-4-ylpyrimidin-5-yl)-amide; as a free base or a salt thereof.

[0472] Formula 18

[0473] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 18. Such compounds are described in the following: International Publication No. WO2004096767A1, published on November 11, 2004, corresponding to International Application No. PCT / DK2004 / 000283, filed on April 23, 2004; U.S. Publication No. US20060264496A1, published on November 23, 2006, corresponding to U.S. Application No. 10 / 551,783, filed on April 23, 2004; the entireties of which are incorporated herein by reference. In the event of any conflict in the context of Formula 18, these references are incorporated herein by reference.

[0474] In one embodiment, the Kv7 channel activator is a compound according to Formula 18:

[0475]

[0476] Wherein, the dotted line represents an optional bond; R 1 and R 1' independently selected from the group consisting of: hydrogen, C1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 1 and R 1' Together with the carbon atom to which it is attached, it forms a 3-8 membered saturated or unsaturated ring optionally containing 1 or 2 heteroatoms; s is 0 or 1; U is O, NR 11 、S、SO2、SO2NR 11 , CO—O or CO—NR 11 ; where R 11 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; or R 2 and R 11 Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; R 2 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl, hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, -NO2, NR 10 R 10' —C 1-6 -Alkyl (ene / yne) group, NR 10 R 10' —C 3-8 -cycloalkyl (alkenyl) and NR 10 R 10' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein R 10 and R 10' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, or R 10 and R 10' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that when R 2 is NO2, halogen or cyano, then s is 0; and provided that when R 2is a hydrogen atom or an acyl group and s is 1, then U is NR 11 , O or S; wherein the group—(U) s —R 2 Attached to position 4 or 6 of indole or indoline; q is 0 or 1; Z is O or S; X is CO or SO2; provided that when X is SO2, q is 0; R 3 Selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl (alkenyl), heterocycloalkyl (alkenyl), C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl) group, C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, Ar, Ar-C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar-heterocycloalkyl (alkenyl), Ar-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), Ar—C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-C 3-8 -cycloalkyl(enyl) group, C 1-6 -alk(ene / ynyl)oxy-heterocycloalk(ene)yl, Ar-oxy-C 1-6 -alk(ene / ynyl), Ar—C 1-6 -alk(en / yn)yloxy-C 1-6 -alk(ene / ynyl) group, C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)oxy-carbonyl-C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy-carbonyl-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8-cycloalkyl (alkenyl), hydroxy-heterocycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl (alkenyl), halogenated heterocycloalkyl (alkenyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl(enyl), halogenated-C 1-6 -Alkyl (ene / alkynyl) -heterocycloalkyl (ene) group, halo-C 1-6 -Alk(ene / ynyl)-Ar, halo-C 3-8 -cycloalkyl (alkenyl)-Ar, halo-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alk(ene / ynyl)-Ar, halo-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (enyl)-Ar, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-heterocycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl), cyano-C 1-6 -Alkyl (ene / ynyl) -heterocycloalkyl (ene) group, acyl -C 1-6 -alk(ene / ynyl), acyl-C 3-8 -cycloalkyl (enyl), acyl-heterocycloalkyl (enyl), acyl-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), acyl-C 1-6 -alk(en / yn)yl-C 3-8 -cycloalkyl (alkenyl) group, acyl-C 1-6 -Alk(ene / ynyl)-heterocycloalk(ene) and -NR 12 R 12' , optionally substituted NR 12 R 12' —C 1-6 -alk(en / yn)yl, optionally substituted NR 12 R12' —C 3-8 -cycloalkyl(enyl), optionally substituted NR 12 R 12' —C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl; wherein R 12 and R 12' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar—C 3-8 -cycloalkyl (alkenyl), Ar—C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), hydroxy-C 1-6 -alk(ene / ynyl), hydroxy-C 3-8 -cycloalkyl (alkenyl), hydroxy-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl) and cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yl, or R 12 and R 12' Together with the nitrogen atom to which it is attached, it forms a 4-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms; provided that when R 3 It is NR 12 R 12' When q is 0; and Y is selected from the group according to the following formula:

[0477]

[0478] wherein W is O or S; T is N, NH or O; L is N, C or CH; a is 0, 1, 2 or 3; b is 0, 1, 2, 3 or 4; c is 0 or 1; d is 0, 1, 2 or 3; e is 0, 1 or 2; f is 0, 1, 2, 3, 4 or 5; g is 0, 1, 2, 3 or 4; h is 0, 1, 2 or 3; j is 0, 1, 2 or 3; provided that when T is a nitrogen atom, then j is 0, 1, 2 or 3; and when T is NH or an oxygen atom, then j is 0, 1 or 2; k is 0, 1, 2, 3 or 4; and each R 5 Independently selected from the group consisting of: C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar, Ar—C 1-6 -alk(ene / ynyl), Ar-thio, Ar-oxy, acyl, C 1-6 -alk(en / yn)yloxy, C 3-8 -cycloalkyl(enyl)oxy, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn)yloxy, halogen, halo-C 1-6 -alk(ene / ynyl), halo-C 3-8 -cycloalkyl(enyl), halogenated-C 3-8 -cycloalkyl(enyl)-C 1-6 -Alkyl (ene / yne) group, -CO-NR 6 R 6' , cyano, cyano-C 1-6 -alk(ene / ynyl), cyano-C 3-8 -cycloalkyl (alkenyl), cyano-C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), -NR 7 R 7' 、—S—R 8 and—SO2R 8 ; or two adjacent R 5 Together with the aromatic group to which it is attached, it forms a 4-8 membered ring optionally containing one or two heteroatoms; R 6 and R 6' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(en / yn) group and Ar; R 7 and R 7' independently selected from the group consisting of: hydrogen, C 1-6-alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 - alk(en / yn)yl, Ar and acyl; and R 8 Selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) group, C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl), Ar and -NR 9 R 9' ; where R 9 and R 9' independently selected from the group consisting of: hydrogen, C 1-6 -alk(ene / ynyl) group, C 3-8 -cycloalkyl(enyl) and C 3-8 -cycloalkyl(enyl)-C 1-6 -alk(ene / ynyl); provided that when R 8 Yes—NR 9 R 9' When R 5 Not—S—R 8 or a salt thereof.

[0479] Formula 19

[0480] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 19. Such compounds are described in U.S. Patent No. 9,248,122, published on February 2, 2016, corresponding to U.S. Application No. 14 / 091,395 filed on November 27, 2013; the reference is incorporated herein by reference in its entirety. In the event of any conflict in the context of Formula 19, this reference is incorporated herein by reference.

[0481] In one embodiment, the Kv7 channel activator is a compound according to Formula 19:

[0482]

[0483] Among them A 1 、A 2 and A 3 Express CR independently of each other 4 ,N,O,S or N(CH3),A 4 Indicates CR 4 or N, and n represents 0 or 1, provided that A 1 、A 2 、A 3 and A 4At least one of them does not represent CR 4 , and the condition is that if n represents 0, then A 1 、A 2 and A 3 Exactly one of represents O, S or N(CH3), or if n represents 1, then A 1 、A 2 and A 3 Express CR independently of each other 4 or N, R 1 Indicates C 1-10 - an aliphatic residue, which is unsubstituted or mono- or polysubstituted; C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted and which is optionally substituted in each case by a C 1-8 -aliphatic radicals; aryl or heteroaryl, which are in each case unsubstituted or monosubstituted or polysubstituted and in each case optionally connected via C 1-8 -aliphatic group connection; R 2 Indicates F; Cl; Br; I; CN; CF3; C(═O)H; NO2; OCF3; SCF3; C 1-4 -aliphatic residue, C(═O)—C 1-4 -aliphatic residue, C(═O)—O—C 1-4 -aliphatic residue, C(═O)—NH—C 1-4 -aliphatic residues, C(═O)—N(C 1-4 -aliphatic residue)2, O—C 1-4 -aliphatic residue, O—C(═O)—C 1-4 -aliphatic residue, S—C 1-4 -aliphatic residue, S(═O)2—C 1-4 -aliphatic residue, S(═O)2—O—C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted; C 3-6 - a cycloaliphatic residue or a 3- to 7-membered heterocycloaliphatic residue, which is in each case unsubstituted or monosubstituted or polysubstituted and which is optionally substituted in each case by a C 1-4 -aliphatic group connection; R 3 Indicates C 2-10 - an aliphatic residue, which is unsubstituted or mono- or polysubstituted; C 3-10- a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted and which is optionally substituted in each case by a C 1-8 -Aliphatic group connection, or represents S-R 5 、O—R 6 or N(R 7 R 8 ), where R 5 and R 6 In each case C 1-10 - an aliphatic residue, which is unsubstituted or mono- or polysubstituted; C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted and which is optionally substituted in each case by a C 1-8 - an aliphatic group, provided that if R 5 or R 6 represents a 3- to 10-membered heteroalicyclic residue, the 3- to 10-membered heteroalicyclic residue is linked via a carbon atom, R 7 Indicates C 1-10 - an aliphatic residue, which is unsubstituted or mono- or polysubstituted; C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted and which is optionally substituted in each case by a C 1-8 - an aliphatic group, provided that if R 7 represents a 3- to 10-membered heteroalicyclic residue, the 3- to 10-membered heteroalicyclic residue is linked via a carbon atom; and R 8 Indicates C 1-10 - an aliphatic residue, which is unsubstituted or mono- or polysubstituted; or R 7 and R 8 Together with the nitrogen atom to which it is attached, it forms a 3- to 10-membered heteroalicyclic residue which is unsubstituted or monosubstituted or polysubstituted; and each R 4 independently represents H, F, Cl, Br, I, CN, CF3, CHF2, CH2F, OCF3, OCHF2, OCH2F, SCF3, O—C 1-4 -aliphatic residues, C 1-4 -aliphatic residue or S(═O)2—C 1-4- an aliphatic residue; wherein "aliphatic group" and "aliphatic residue" may in each case be branched or unbranched, saturated or unsaturated, wherein "alicyclic residue" and "heteroalicyclic residue" may in each case be saturated or unsaturated, wherein "aliphatic residue", "alicyclic residue" and "heteroalicyclic residue" are "monosubstituted or polysubstituted" with respect to "aliphatic group", and with respect to the corresponding residue or group, one or more hydrogen atoms are each independently substituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, NH—C(═O)—C 1-4 Aliphatic residues, N(C 1-4 Aliphatic residue)-C(═O)—C 1-4 Aliphatic residue, NH—S(═O)2—C 1-4 Aliphatic residues, N(C 1-4 Aliphatic residue)-S(═O)2—C 1-4 Aliphatic residues, ═O, OH, OCF3, O—C 1-4 -aliphatic residue, O—C(═O)—C 1-4 -Aliphatic residues, SH, SCF3, S—C 1-4 -aliphatic residues, S(═O)2OH, S(═O)2—C 1-4 -aliphatic residue, S(═O)2—O—C 1-4 -aliphatic residue, S(═O)2—NH(C 1-4 -aliphatic residues), S(═O)2—N(C 1-4 -aliphatic residues)2, CN, CF3, CHO, COOH, C 1-4 -aliphatic residue, C(═O)—C 1-4 -aliphatic residue, C(═O)—O—C 1-4 -aliphatic residues, C 3-6 -alicyclic residues, 3- to 7-membered heteroalicyclic residues, C(═O)NH2, C(═O)—NH(C 1-4 -aliphatic residues) and C(═O)—N(C 1-4 -aliphatic residue) 2; wherein, with respect to "aryl" and "heteroaryl", "mono- or polysubstituted" refers to one or more hydrogen atoms each independently of one another being substituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, NH—C(═O)—C1-4 -aliphatic residues, N(C 1-4 Aliphatic residue)-C(═O)—C 1-4 Aliphatic residue, NH—S(═O)2—C 1-4 Aliphatic residues, N(C 1-4 Aliphatic residue)-S(═O)2—C 1-4 Aliphatic residue, OH, OCF3, O—C 1-4 -aliphatic residue, O—C(═O)—C 1-4 -Aliphatic residues, SH, SCF3, S—C 1-4 -aliphatic residues, S(═O)2OH, S(═O)2—C 1-4 -aliphatic residue, S(═O)2—O—C 1-4 -aliphatic residue, S(═O)2—NH(C 1-4 -aliphatic residues), S(═O)2—N(C 1-4 -aliphatic residues)2、CN、CF3、C(═O)H、C(═O)OH、C 1-4 -aliphatic residue, C(═O)—C 1-4 -aliphatic residue, C(═O)—O—C 1-4 -aliphatic residues, C 3-6 -alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, aryl, heteroaryl, C(═O)NH2, C(═O)—NH(C 1-4 -aliphatic residues) and C(═O)—N(C 1-4 -aliphatic residue) 2; in the form of an individual stereoisomer or a mixture of stereoisomers in any mixing ratio, and / or in the form of a free compound, a solvate and / or a physiologically acceptable salt.

[0484] In another embodiment, A 1 、A 2 and A 3 Express CR independently of each other 4 ,N,O,S or N(CH3),A 4 Indicates CR 4 or N, and n represents 0 or 1, provided that A 1 、A 2 、A 3 and A 4 At least one of them does not represent CR 4 , and the condition is that if n represents 0, then A 1 、A 2 and A 3 Exactly one of represents O, S or N(CH3), or if n represents 1, then A 1 、A2 and A 3 Express CR independently of each other 4 or N, R 1 Indicates C 1-10 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue, C(═O)—OH, C 3-8 - alicyclic residues and 3- to 7-membered heteroalicyclic residues, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-8 - the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4-Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein the C 3-10 - the cycloaliphatic residue or the 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-8 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 - an aliphatic residue and C(═O)OH, or an aryl or heteroaryl radical, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, O 3-8 - alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4 -aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C1-4 - aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, and wherein said C 3-6 - the cycloaliphatic residue and the 3- to 7-membered heterocycloaliphatic residue may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH, and wherein the aryl or heteroaryl residues may in each case optionally be C substituted by at least one substituent selected from the group consisting of: 1-8 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -aliphatic residues, CF3, CN and C(═O)OH, R 2 Indicates F, Cl, Br, I, CN, CF3, NO2, OCF3, SCF3, and C 1-4 -aliphatic residue, S—C 1-4 -aliphatic residue, O—C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - aliphatic residues,

[0485] or

[0486] C 3-6 - a cycloaliphatic residue or a 3- to 7-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted and in each case optionally substituted by C 1-4 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4-aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -aliphatic residues, CF3, CN and C(═O)OH, R 3 Indicates C 2-10 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - aliphatic residues,

[0487] or

[0488] Indicates C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 The aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-8-Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 - aliphatic residues and C(═O)OH,

[0489] or

[0490] Indicates S-R 5 、O—R 6 or N(R 7 R 8 ), where R 5 and R 6 In each case C 1-10 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, or in each case C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue, C(═O)—OH, C 3-8 - alicyclic residues and 3- to 7-membered heteroalicyclic residues, wherein the C 1-4- the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-8 - the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein the C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-8 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH, provided that if R 5 or R 6 represents a 3- to 10-membered heteroalicyclic residue, the 3- to 10-membered heteroalicyclic residue is linked via a carbon atom, R 7 Indicates C 1-10 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue, C(═O)—O—C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4- the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and unsubstituted O—C 1-4 -aliphatic residue, or represents C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C(═O)—O—C 1-4 -aliphatic residues, C 3-6 - alicyclic residues and 3- to 7-membered heteroalicyclic residues, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein said C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-0 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -aliphatic residue, C(═O)—O—C 1-4-Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH, provided that if R 7 represents a 3- to 10-membered heteroalicyclic residue, the 3- to 10-membered heteroalicyclic residues are linked via carbon atoms,

[0491] and / or

[0492] R 8 Indicates C 1-10 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - aliphatic residues,

[0493] or

[0494] R 7 and R 8 Together with the nitrogen atom to which it is attached, it forms a 3- to 10-membered heteroalicyclic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue, C(═O)—OH, C 3-6 - alicyclic residues and 3- to 7-membered heteroalicyclic residues, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - aliphatic residues,

[0495] and / or

[0496] wherein the C 3-6 - the cycloaliphatic residue and the 3- to 7-membered heterocycloaliphatic residue may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein R 7 and R 8 The 3- to 10-membered heteroalicyclic residue formed together with the nitrogen atom to which it is attached can optionally be condensed with an aryl or heteroaryl group, wherein the aryl or heteroaryl residue condensed in this way can itself be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, C 3-6 - alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4-aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 - aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, and wherein said C 3-6 The alicyclic residues and the 3- to 7-membered heteroalicyclic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)—OH, and each R 4 independently represent H, F, Cl, Br, I, CN, CF3, CHF2, CH2F, OCF3, OCHF2, OCH2F, SCF3, O—C 1-4 -aliphatic residues, C 1-4 -aliphatic residue or S(═O)2—C 1-4 - an aliphatic residue.

[0497] In another embodiment, n represents 1 and A 1 Indicates N, A 2 Indicates CR 4 、A 3 Indicates CR 4 And A 4 Indicates CR 4 ; or n represents 1 and A 1 Indicates CR 4 、A 2 Indicates N, A 3 Indicates CR 4 And A 4 Indicates CR 4 ; or n represents 1 and A 1 Indicates CR 4 、A 2 Indicates CR 4 、A 3 Indicates N and A 4 Indicates CR 4 ; or n represents 1 and A 1 Indicates CR 4 、A 2 Indicates CR 4 、A3 Indicates CR 4 And A 4 represents N; or n represents 1 and A 1 Indicates N, A 2 Indicates N, A 3 Indicates CR 4 And A 4 Indicates CR 4 ; or n represents 1 and A 1 Indicates N, A 2 Indicates CR 4 、A 3 Indicates N and A 4 Indicates CR 4 ; or n represents 1 and A 1 Indicates N, A 2 Indicates CR 4 、A 3 Indicates CR 4 And A 4 represents N; or n represents 1 and A 1 Indicates CR 4 、A 2 Indicates N, A 3 Indicates N and A 4 Indicates CR 4 ; or n represents 1 and A 1 Indicates CR 4 、A 2 Indicates N, A 3 Indicates CR 4 And A 4 represents N; or n represents 1 and A 1 Indicates CR 4 、A 2 Indicates CR 4 、A 3 Indicates N and A 4 represents N; or n represents 0 and A 1 Indicates CR 4 、A 2 Indicates CR 4 , and A 3 represents S; or n represents 0 and A 1 Indicates N, A 2 Indicates CR 4 And A 3 represents S; or n represents 0 and A 1 Indicates S, A 2 Indicates CR 4 And A 3 Indicates CR 4 ; or n represents 0 and A 1 Indicates S, A 2 Indicates CR 4 And A3 Indicates N.

[0498] In another embodiment, R 2 Indicates F, Cl, Br, I, CN, CF3, NO2, OCF3, SCF3, and C 1-4 -aliphatic residue, S—C 1-4 -aliphatic residue or O—C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, ═O, OH and O—C 1-4 - an aliphatic residue.

[0499] In another embodiment, R 2 Indicates C 1-4 - an aliphatic residue.

[0500] In another embodiment, each R 4 independently represents H, F, Cl, Br, CN, CF3, OCF3, CH3, OCH3 or S(═O)2CH3.

[0501] In another embodiment, R 1 Represents a partial structure:

[0502]

[0503] Where m represents 0, 1 or 2, R 1a and R 1b Each independently represents H, F, Cl, Br, I, O—C 1-4 -aliphatic residue or C 1-4 -aliphatic residue, R 1c Indicates C 1-4 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, O—C 1-4 -Aliphatic residues, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, O—C 1-4-Aliphatic residues, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, CF3 and O—C 1-4 - an aliphatic residue, or represents an aryl or heteroaryl group, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C 3-6 - an alicyclic residue, a 3- to 7-membered heteroalicyclic residue, a benzyl group, a phenyl group, a thienyl group or a pyridyl group, wherein the benzyl group, the phenyl group, the thienyl group and the pyridyl group may each be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 - aliphatic residues, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, and wherein said C 3-6 The alicyclic residues and the 3- to 7-membered heteroalicyclic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, CF3, C 1-4 -aliphatic residues and C(═O)OH.

[0504] In another embodiment, m represents 1 or 2, R 1a and R 1b Indicates H, R 1c Indicates C 1-4 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, O—C 1-4 -Aliphatic residues, CF3 and C 1-4 -aliphatic residue, or represents C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, O—C 1-4 -Aliphatic residues, CF3 and C 1-4- an aliphatic residue, or m represents 0, and R 1c represents an aryl or heteroaryl radical, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C 3-6 - an alicyclic residue, a 3- to 7-membered heteroalicyclic residue, a benzyl group, a phenyl group, a thienyl group or a pyridyl group, wherein the benzyl group, the phenyl group, the thienyl group and the pyridyl group may each be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, and wherein said C 3-6 The alicyclic residues and the 3- to 7-membered heteroalicyclic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, CF3, C 1-4 -aliphatic residues and C(═O)OH.

[0505] In another embodiment, R 3 Indicates C 2-6 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which in each case may be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, OH, ═O, O—C 1-4-aliphatic residues, OCF3, SCF3, (═O)—O—C 1-4 -aliphatic residue, S—C 1-4 -aliphatic residues, CF3, CN and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-7 - a cycloaliphatic residue or a 3- to 7-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN and C 1-4 - an aliphatic residue, or R 3 Indicates S-R 5 or O—R 6 , where R 5 and R 6 In each case C 1-8 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -aliphatic residues, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residues)2, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, CF3 and O—C 1-4 - an aliphatic residue, or in each case C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4- the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue may be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN and C 1-4 - an aliphatic residue, provided that if R 5 or R 6 represents a 3- to 7-membered heteroalicyclic residue, the 3- to 7-membered heteroalicyclic residue is linked via a carbon atom, or R 3 Indicates N(R 7 R 8 ), where R 7 Indicates C 1-6 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - alicyclic residues or 3- to 7-membered heteroalicyclic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, OH, ═O, O—C1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN and C 1-4 - an aliphatic residue, provided that if R 7 represents a 3- to 7-membered heteroalicyclic residue, the 3- to 7-membered heteroalicyclic residue is linked via a carbon atom, and R 8 Indicates C 1-6 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 - aliphatic residue, or R 7 and R 8 Together with the nitrogen atom to which it is attached, it forms a 3- to 10-membered heteroalicyclic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, CF3 and O—C 1-4 - an aliphatic residue, and wherein R 7 and R 8 The 3- to 10-membered heteroalicyclic residue formed together with the nitrogen atom to which it is attached may optionally be condensed with an aryl or heteroaryl group, wherein the aryl or heteroaryl residue condensed in this way may itself be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, ON, C 1-4 -aliphatic residues, C(═O)OH, C 3-6 alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, phenyl, thienyl and pyridyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4- aliphatic residues, wherein benzyl, phenyl, thienyl and pyridyl may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, O—C 1-4 -Aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SCF3, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein the C 3-6 - the alicyclic residues and the 3- to 7-membered heteroalicyclic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH.

[0506] In another embodiment, R 3 Indicates C 2-6 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 -aliphatic residue, or represents C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 -Aliphatic residues may in each case be unsubstituted or replaced by OH or O—C 1-4 - aliphatic residues are mono- or polysubstituted, and wherein the C 3-6 - a cycloaliphatic residue or a 3- to 7-membered heterocycloaliphatic residue can in each case optionally be C 1-4 -aliphatic group link, or R 3 Indicates S-R 5 or O—R 6 , where R 5 and R 6 represents in each case a C which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of 1-6 -Aliphatic residues: F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4- an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 - aliphatic residue, or in each case a C residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of 3-6 -alicyclic residue or 3- to 7-membered heteroalicyclic residue: F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue in each case via an unsubstituted C 1-4 - an aliphatic group, provided that if R 5 or R 6 represents a 3- to 7-membered heteroalicyclic residue, the 3- to 7-membered heteroalicyclic residue is linked via a carbon atom, or R 3 Indicates N(R 7 R 8 ), where R 7 represents a C which is unsubstituted or mono- or poly-substituted by at least one substituent selected from the group consisting of 1-6 -Aliphatic residues: F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4- the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue in each case via an unsubstituted C 1-4 - an aliphatic group, provided that if R 7 represents a 3- to 7-membered heteroalicyclic residue, the 3- to 7-membered heteroalicyclic residue is linked via a carbon atom, and R 8 represents unsubstituted C 1-4 - an aliphatic residue, or R 7 and R 8 Together with the nitrogen atom to which it is attached, it forms a 3- to 7-membered heteroalicyclic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 - an aliphatic residue, and wherein R 7 and R 8 The 3- to 7-membered heteroalicyclic residue formed together with the nitrogen atom to which it is attached can optionally be condensed with a phenyl or pyridyl residue, wherein the phenyl or pyridyl residue condensed in this way can itself be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, benzyl, phenyl and pyridyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH and O—C 1-4 - an aliphatic residue, wherein benzyl, phenyl and pyridine may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OCH3, OCF3, OCH2CH2OH, OCH2CH2OCH3, SCF3, CF3, C 1-4 - an aliphatic residue.

[0507] In another embodiment, A1 、A 2 and A 3 Express CR independently of each other 4 ,N,O,S or N(CH3),A 4 Indicates CR 4 or N, and n represents 0 or 1, provided that A 1 、A 2 、A 3 and A 4 At least one of them does not represent CR 4 , and the condition is that if n represents 0, then A 1 、A 2 and A 3 Exactly one of represents O, S or N(CH3), or if n represents 1, then A 1 、A 2 and A 3 Express CR independently of each other 4 or N, R 1 Represents a partial structure:

[0508]

[0509] Where: m represents 0, 1 or 2, R 1a and R 1b Each independently represents H, F, Cl, O—C 1-4 -aliphatic residue or C 1-4 -aliphatic residue, R 1c Indicates C 1-4 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, C 1-10 —C 1-4 -Aliphatic residues, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, C 1-10 —C 1-4 -Aliphatic residues, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4- the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, CF3 and O—C 1-4 - an aliphatic residue, or represents an aryl or heteroaryl group, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C 3-6 - an alicyclic residue, a 3- to 7-membered heteroalicyclic residue, a benzyl group, a phenyl group, a thienyl group or a pyridyl group, wherein the benzyl group, the phenyl group, the thienyl group and the pyridyl group may each be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C 1-4 -Aliphatic residues, OCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, and wherein said C 3-6 The alicyclic residues and the 3- to 7-membered heteroalicyclic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, CF3, C 1-4 -aliphatic residues and C(═O)OH, R 2 Indicates F, Cl, Br, I, CN, CF3, NO2, OCF3, SCF3, and C 1-4 -aliphatic residue, S—C 1-4 -aliphatic residue or O—C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, ═O, OH and O—C 1-4 -aliphatic residue, R 3 represents a C which is unsubstituted or mono- or poly-substituted by at least one substituent selected from the group consisting of 2-6 -Aliphatic residues: F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 -aliphatic residue, or represents C 3-10- a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 -Aliphatic residues may in each case be unsubstituted or replaced by OH or O—C 1-4 - aliphatic residues are mono- or polysubstituted, and wherein the C 3-10 -Alicyclic residues or 3- to 10-membered heteroalicyclic residues can in each case optionally be C 1-4 -aliphatic group link, or R 3 Indicates S-R 5 or O—R 6 , where R 5 and R 6 In each case C 1-8 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 - an aliphatic residue, or in each case C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - a cycloaliphatic residue or a 3- to 7-membered heterocycloaliphatic residue, in each case by an unsubstituted C 1-4 - an aliphatic group, provided that if R 5 or R 6 represents a 3- to 7-membered heteroalicyclic residue, the 3- to 7-membered heteroalicyclic residue is linked via a carbon atom, or R3 N(R 7 R 8 ), where R 7 Indicates C 1-8 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -aliphatic residues, OCF3, SCF3, C(═O)—O—C 1-4 -Aliphatic residues, CF3 and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - an alicyclic residue or a 3- to 7-membered heteroalicyclic residue in each case via an unsubstituted C 1-4 - an aliphatic group, provided that if R 7 represents a 3- to 7-membered heteroalicyclic residue, the 3- to 7-membered heteroalicyclic residue is linked via a carbon atom, and R 8 represents unsubstituted C 1-4 - aliphatic residue, or R 7 and R 8 Together with the nitrogen atom to which it is attached, it forms a 3- to 7-membered heteroalicyclic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN and C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, CF3 and O—C 1-4- an aliphatic residue, and wherein R 7 and R 8 The 3- to 7-membered heteroalicyclic residue formed together with the nitrogen atom to which it is attached can optionally be condensed with a phenyl or pyridyl residue, wherein the phenyl or pyridyl residue condensed in this way can itself be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH, O—C 1-4 -Aliphatic residues, OCF3, SCF3, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, benzyl, phenyl and pyridyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OH and O—C 1-4 - an aliphatic residue, wherein benzyl, phenyl and pyridyl may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, OCH3, OCF3, OCH2CH2OH, OCH2CH2OCH3, SH, SCF3, CF3 and C 1-4 - an aliphatic residue; and each R 4 independently represent H, F, Cl, Br, CN, CF3, OCF3, CH3, OCH3 or S(═O)2CH3.

[0510] In further embodiments, the Kv7 channel activator is selected from the group consisting of: 1 2-ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,5]naphthyridine-3-carboxylic acid amide; 2 2-ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,5]naphthyridine-3-carboxylic acid amide; 3-ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,6]naphthyridine-3-carboxylic acid amide; 4 2-ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,6]naphthyridine-3-carboxylic acid amide; 5 2-Ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,7]naphthyridine-3-carboxamide; 6-Ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,7]naphthyridine-3-carboxamide; 7 2-Ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,8]naphthyridine-3-carboxamide; 8 2-Ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,8]naphthyridine-3-carboxamide; 9 2-Ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,8]naphthyridine-3-carboxamide; 10 2-Ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,8]naphthyridine-3-carboxamide; 11 2-Ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,6]naphthyridine-3-carboxamide; 12 2-Ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,6]naphthyridine-3-carboxamide; 13 2-Ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,5]naphthyridine-3-carboxamide; 14 2-Ethylthio-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,5]naphthyridine-3-carboxamide; 15 5-Ethylthio-N-[(3-fluorophenyl)-methyl]-7-methyl-thieno[3,2-b]pyridine-6-carboxylic acid amide; 16 6-Ethylthio-N-[(3-fluorophenyl)-methyl]-4-methyl-thieno[2,3-b]pyridine-5-carboxylic acid amide; 17 5-Ethoxy-N-[(3-fluorophenyl)-methyl]-7-methyl-2-(trifluoromethyl)-thieno[3,2-b]pyridine-6-carboxylic acid amide; 18 6-Ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-2-(trifluoromethyl)-thieno[2,3-b]pyridine-5-carboxylic acid amide; in the form of free compounds, solvates and / or physiologically acceptable salts.

[0511] Formula 20

[0512] In one embodiment, the Kv7 channel activator can be selected from one of the following compounds according to Formula 20. Such compounds are described in the following: U.S. Patent No. 9,284,286, issued on March 15, 2016, corresponding to U.S. Application No. 14 / 091.373, filed on November 27, 2013; International Publication No. WO2014082737A1, published on June 5, 2014, corresponding to International Application No. PCT / EP2013 / 003572, filed on November 27, 2013; the entireties of which are incorporated herein by reference. In the event of any conflict in the context of Formula 20, these references are incorporated herein by reference.

[0513] In one embodiment, the Kv7 channel activator is a compound according to Formula 20:

[0514]

[0515] Among them: A 1 Indicates CR 10 R 11 or S; A 2 Indicates CR 12 R 13 , C(═O), O, S, S(═O) or S(═O)2; A 3 、A 4 and A 5 Express CR independently of each other 7 , N, O, S or NR 8 , A 6 Indicates CR 7 or N, and n represents 0 or 1, provided that if n represents 0, then A 3 、A 4 and A 5 Exactly one of represents O, S or NR 8 , or if n is 1, then A 3 、A 4 and A 5 Express CR independently of each other 7 or N; and provided that if n represents 1 and A 3 、A 4 and A 5 Each represents CR 7 , then A 6 Does not mean N; R 1 Indicates C 1-10 - an aliphatic residue, which is unsubstituted or mono- or polysubstituted; C 3-10- a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue, which is in each case unsubstituted or mono- or polysubstituted and which is optionally substituted in each case by a C 1-4 -aliphatic radicals; aryl or heteroaryl, which are in each case unsubstituted or monosubstituted or polysubstituted and in each case optionally connected via C 1-4 -aliphatic group connection; R 2 、R 3 ; R 4 、R 5 、R 10 、R 11 、R 12 and R 13 Each independently represents H; F; Cl; Br; I; NO2; CF3; CN; OH; OCF3; SH; SCF3; C 1-10 -aliphatic residue, O—C 1-10 -aliphatic residue or S—C 1-10 - an aliphatic residue, which is in each case saturated or unsaturated, branched or unbranched, unsubstituted or monosubstituted or polysubstituted; or C 3-10 - an alicyclic residue, which is saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted; or R 2 and R 3 or R 4 and R 5 or R 10 and R 11 or R 12 and R 13 or R 2 and R 11 or R 2 and R 4 or R 2 and R 13 or R 4 and R 13 or R 4 and R 11 or R 12 and R 13 Together with the carbon atom it is attached to, it forms C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case saturated or unsaturated, unsubstituted or monosubstituted or polysubstituted; wherein the remaining substituents R 2 、R 3 ; R 4 ; R 5 ; R 10 、R 11 、R 12 and R13 has in each case the meaning given above; R 6 Indicates C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case saturated or unsaturated, unsubstituted or monosubstituted or polysubstituted; or represents an aryl or heteroaryl residue, which is in each case unsubstituted or monosubstituted or polysubstituted; each R 7 independently represent H, F; Cl; CN; CF3; CHF2; CH2F; OCF3; OCHF2; OCH2F; SCF3; O—C 1-4 -aliphatic residues, C 1-4 -aliphatic residue or S(═O)2—C 1-4 - an aliphatic residue, wherein the C 1-4 - the aliphatic residue is in each case saturated or unsaturated, branched or unbranched, unsubstituted or monosubstituted or polysubstituted; and R 8 Indicates H or C 1-4 - an aliphatic residue, wherein the aliphatic residue may be saturated or unsaturated, branched or unbranched, unsubstituted or monosubstituted or polysubstituted; wherein "aliphatic group" and "aliphatic residue" may in each case be branched or unbranched, saturated or unsaturated, wherein "alicyclic residue" and "heteroalicyclic residue" may in each case be saturated or unsaturated, wherein "monosubstituted or polysubstituted" with respect to "aliphatic group", "aliphatic residue", "alicyclic residue" and "heteroalicyclic residue" refer to one or more hydrogen atoms each independently of one another being substituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, NH—C(═O)—C 1-4 Aliphatic residues, N(C 1-4 Aliphatic residue)-C(═O)—C 1-4 Aliphatic residue, NH—S(═O)2—C 1-4 Aliphatic residues, N(C 1-4 Aliphatic residue)-S(═O)2—C 1-4 Aliphatic residues, ═O, OH, OCF3, O—C 1-4 -aliphatic residue, O—C(═O)—C 1-4 -Aliphatic residues, SH, SCF3, S—C 1-4 -aliphatic residues, S(═O)2OH, S(═O)2—C 1-4 -aliphatic residue, S(═O)2—O—C 1-4 -aliphatic residue, S(═O)2—NH(C1-4 -aliphatic residues), S(═O)2—N(C 1-4 -aliphatic residues)2, CN, CF3, CHO, COOH, C 1-4 -aliphatic residue, C(═O)—C 1-4 -aliphatic residue, C(═O)—O—C 1-4 -aliphatic residues, C 3-6 -alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, aryl, heteroaryl, C(═O)NH2, C(═O)—NH(C 1-4 -aliphatic residues) and C(═O)—N(C 1-4 -aliphatic residue) 2; wherein, with respect to "aryl" and "heteroaryl", "mono- or polysubstituted" refers to one or more hydrogen atoms each independently of one another being substituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, NH—C(═O)—C 1-4 -aliphatic residues, N(C 1-4 Aliphatic residue)-C(═O)—C 1-4 Aliphatic residue, NH—S(═O)2—C 1-4 Aliphatic residues, N(C 1-4 Aliphatic residue)-S(═O)2—C 1-4 Aliphatic residue, OH, OCF3, O—C 1-4 -aliphatic residue, O—C(═O)—C 1-4 -Aliphatic residues, SH, SCF3, S—C 1-4 -aliphatic residues, S(═O)2OH, S(═O)2—C 1-4 -aliphatic residue, S(═O)2—O—C 1-4 -aliphatic residue, S(═O)2—NH(C 1-4 -aliphatic residues), S(═O)2—N(C 1-4 -aliphatic residues)2、CN、CF3、C(═O)H、C(═O)OH、C 1-4 -aliphatic residue, C(═O)—C 1-4 -aliphatic residue, C(═O)—O—C 1-4 -aliphatic residues, C 3-6 -alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, aryl, heteroaryl, C(═O)NH2, C(═O)—NH(C 1-4 -aliphatic residues) and C(═O)—N(C 1-4-aliphatic residue) 2; in the form of an individual stereoisomer or a mixture of stereoisomers in any mixing ratio, and / or in the form of a free compound, a solvate and / or a physiologically acceptable salt.

[0516] In another embodiment, A 1 Indicates CR 10 R 11 or S; A 2 Indicates CR 12 R 13 , C(═O), O, S, S(═O) or S(═O)2; A 3 、A 4 and A 5 Express CR independently of each other 7 , N, O, S or NR 8 , A 6 Indicates CR 7 or N, and n represents 0 or 1, provided that if n represents 0, then A 3 、A 4 and A 5 Exactly one of represents O, S or NR 8 , or if n is 1, then A 3 、A 4 and A 5 Express CR independently of each other 7 or N; and provided that if n represents 1 and A 3 、A 4 and A 5 Each represents CR 7 , then A 6 Does not mean N; R 1 Indicates C 1-10 - an aliphatic residue which is unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 -aliphatic residue, or represents C 3-10- an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C 3-6 - alicyclic residues and 3- to 7-membered heteroalicyclic residues, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein said C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 - an aliphatic residue and C(═O)OH, or an aryl or heteroaryl radical, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C1-4 -aliphatic residue)2, OH, O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C 3-6 alicyclic residues, 3- to 6-membered heteroalicyclic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4 -aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, and wherein said C 3-6 - the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH, and wherein the aryl or heteroaryl residues may in each case optionally be C substituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, Br, NO2, NH2, NH(C 1-4-aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -aliphatic residues, CF3, CN and C(═O)OH, R 2 、R 3 、R 5 、R 10 、R 11 、R 12 and R 13 Each represents H, F, Cl, Br, I, NO2, CF3, CN, OH, OCF3, SH, SCF3, C independently of the others 1-4 -aliphatic residue, O—C 1-4 -aliphatic residue or S—C 1-4 - an aliphatic residue, which is in each case saturated or unsaturated, branched or unbranched, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 -aliphatic residues, or C 3-10 - a cycloaliphatic residue, which is saturated or unsaturated, branched or unbranched, in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-10 - cycloaliphatic residues may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4-aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH, or R 2 and R 3 or R 4 and R 5 or R 10 and R 11 or R 12 and R 13 or R 2 and R 11 or R 2 and R 4 or R 2 and R 13 or R 4 and R 13 or R 4 and R 11 or R 12 and R 13 Together with the carbon atoms to which it is attached, it forms C which is in each case saturated or unsaturated and in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of 3-10 - alicyclic residues or 3- to 10-membered heteroalicyclic residues: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4-Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein the remaining substituents R 2 、R 3 、R 4 、R 5 、R 10 、R 11 、R 12 and R 13 has in each case the meaning given above; R 6 Indicates C 3-10 - an alicyclic residue or a 3- to 10-membered heteroalicyclic residue, which is in each case saturated or unsaturated and in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C 3-6 - alicyclic residues and 3- to 7-membered heteroalicyclic residues, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, and wherein said C 3-6 - the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residue and C(═O)OH, and wherein said C 3-10 - a cycloaliphatic residue or a 3- to 10-membered heterocycloaliphatic residue may in each case optionally be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: 1-4-Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 - an aliphatic residue and C(═O)OH, or an aryl or heteroaryl radical, which is in each case unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C 3-6 - alicyclic residues, 3- to 7-membered heteroalicyclic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C 1-4 - the aliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and O—C 1-4 - an aliphatic residue, wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2, OH, O—C 1-4 -aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 - aliphatic residues, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3 and C(═O)OC2H5, and wherein said C 3-6- the cycloaliphatic residues and the 3- to 7-membered heterocycloaliphatic residues may in each case be unsubstituted or mono- or polysubstituted by at least one substituent selected from the group consisting of: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic residue)2、OH、═O、O—C 1-4 -Aliphatic residues, OCF3, SH, SCF3, S—C 1-4 -Aliphatic residues, CF3, CN, C 1-4 -aliphatic residues and C(═O)OH, and wherein the aryl or heteroaryl residues may in each case optionally be C substituted by at least one substituent selected from the group consisting of: 1-4 -Aliphatic group connection: F, Cl, Br, I, NO2, NH2, NH(C 1-4 -aliphatic residues), N(C 1-4 -aliphatic resid...

Claims

A pharmaceutical composition comprising a metal channel activator and an NMDA receptor antagonist.

2. The pharmaceutical composition according to claim 1, wherein the metal channel activator is a potassium channel activator.

3. The pharmaceutical composition according to claim 2, wherein the potassium channel activator is a Kv7 channel activator.

4. The pharmaceutical composition of claim 3, wherein the Kv7 channel activator is a Kv7.1 channel activator, a Kv7.2 channel activator, a Kv7.3 channel activator, a Kv7.4 channel activator, a Kv7.5 channel activator, or any combination thereof.

5. The pharmaceutical composition according to claim 3 or 4, wherein the Kv7 channel activator is a Kv7.2 / 7.3 channel activator.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the metal channel activator is selected from one or more compounds according to any one or more of Formulas 1 to 171.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the NMDA receptor antagonist is selected from one or more compounds according to any one or more of formulas 200 to 260.

8. The pharmaceutical composition according to any one of claims 1 to 5, wherein the NMDA receptor antagonist is selected from one or more compounds according to any one or more of Formulas 200 to 260, and wherein the metal channel activator is selected from one or more disclosed compounds according to any one or more of Formulas 1 to 171.

9. according to the pharmaceutical composition described in any one of claims 1 to 8, wherein the metal channel activator is 10. according to the pharmaceutical composition described in any one of claims 1 to 8, wherein said metal channel activator is 11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the NMDA receptor antagonist is ketamine, lanicemine, dextromethorphan (DXM), phencyclidine (PCP), methamphetamine (MXE) or a pharmaceutically acceptable salt thereof. 12 . The pharmaceutical composition according to claim 1 , wherein the NMDA receptor antagonist or a pharmaceutically acceptable salt thereof is in the form of a prodrug.

13. The pharmaceutical composition according to any one of claims 1 to 12, wherein the NMDA receptor antagonist is lanisamine or a pharmaceutically acceptable salt thereof.

14. The pharmaceutical composition according to claim 13, wherein the lanisigmine or a pharmaceutically acceptable salt thereof is in the form of a prodrug.

15. The pharmaceutical composition according to claim 14, wherein the prodrug of lanisimine has the following structure: Where R1 is C 1-6 Alkyl C(O)O(C 1-6 alkoxy), or AA is a natural amino acid linked by peptide bonds; or a pharmaceutically acceptable salt thereof.

16. The pharmaceutical composition according to claim 14 or 15, wherein the prodrug of lanisimide has the following structure: or a pharmaceutically acceptable salt thereof.

17. A method of treating a depressive disorder, comprising administering the pharmaceutical composition according to any one of claims 1 to 17.

18. The method of claim 17, wherein the depressive disorder is major depressive disorder (MDD), disruptive mood dysregulation disorder, persistent depressive disorder, bipolar spectrum disorder, postpartum depression, premenstrual dysphoric disorder (PMDD), seasonal affective disorder (SAD), atypical depression, treatment-resistant depression (TRD), depression associated with agitation or anxiety, adjustment disorder with depressed mood, prolonged depressive reaction, or a combination thereof.

19. A method of treating a neurological or neurodegenerative disorder comprising administering a pharmaceutical composition according to any one of claims 1 to 16.

20. The method of claim 19, wherein the neurological or neurodegenerative disorder is amyotrophic lateral sclerosis, bipolar disorder, treatment-resistant and major depressive disorder, generalized anxiety disorder, panic disorder, social anxiety, mood disorders, cognitive disorders, dementia, agitation, apathy, psychosis, post-traumatic stress disorder, irritability, disinhibition, learning disabilities, memory loss, personality disorders, bipolar disorder, Rett syndrome, syndrome), eating disorders, conduct disorders, neurodegenerative disorders, pain disorders, supranuclear palsy, frontotemporal dementia, frontotemporal lobar degeneration, delirium, Alzheimer's disease, mild cognitive impairment, mild cognitive impairment due to Alzheimer's disease, drug addiction, tinnitus, mental retardation, obsessive-compulsive disorder, spinal muscular atrophy, radiation therapy, multiple sclerosis, chronic cerebellar ataxia, cervical spondylotic myelopathy, spinal cord injury, hereditary cerebellar ataxia, Tourette syndrome, autism spectrum disorder, schizophrenia, fragile X syndrome, Parkinson's disease, Huntington's disease, or any combination thereof.

21. A method of treating a pain disorder comprising administering a pharmaceutical composition according to any one of claims 1 to 16.

22. The method of claim 21, wherein the pain disorder is acute pain, chronic pain, neuropathic pain, nociceptive pain and / or radicular pain.

23. The method of claim 21, wherein the pain disorder is migraine, inflammatory pain, persistent pain, cancer pain, and / or postoperative pain.

24. A kit for treating a patient suffering from a condition clinically relevant to a metal channel activator, the kit comprising: (a) the metal channel activator; as well as (b) instructions for administering the metal channel activator in combination with an NMDA receptor antagonist by one of the methods according to claims 17 to 23.

25. A kit for treating a patient suffering from a condition clinically relevant to an NMDA receptor antagonist, the kit comprising: (a) the NMDA receptor antagonist; as well as (b) instructions for administering the NMDA receptor antagonist together with the metal channel activator by one of the methods according to claims 17 to 23.

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