Combination therapies including metal channel activators and NMDA receptor antagonists

Abstract

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

Description

COMBINATION THERAPIES INCLUDING METAL CHANNEL ACTIVATORS AND NMDA RECEPTOR ANTAGONISTS CROSS-REFERENCE TO RELATED APPLICATION

[0001] This International Patent Application claims priority to United States Provisional Patent Application No.63 / 402,416, filed August 30, 2022, which is incorporated by reference in its entirety herein. TECHNICAL FIELD

[0002] The present invention relates to combination therapies for treatment of various medical conditions. Specifically, the present invention relates to a combination of a metal channer activator and N-methyl-D-aspartate (NMDA) receptor antagonists for treatment of neurological and neurodegenerative disorders. BACKGROUND

[0003] Metal channel activators (openers) are associated with a wide range of physiological functions including the regulation of the electrical properties of excitable cells. Metal channels control the follow of metal ions such as Potassium (K+) and Sodium (Na+) across a cell membrane. A primary function of these channels in the brain is to regulate the neuronal action potential. Several neurologic disorders are potentially due to dysregulation of metal channels.

[0004] Potassium (K+) channels, present on the plasma membranes of most cell types, are the most diverse class of all ion channels. Potassium channels of the Kv7 family of voltage-gated potassium (K+) channels are of particular therapeutic interest due to their importance in neurological conditions such as excitability disorders including Amyotrophic lateral sclerosis (ALS). There are five members of the Kv7 family of voltage-gated potassium (K+) channels, including Kv7.1, Kv7.2, Kv7.3, Kv7.4, and Kv7.5.

[0005] Metal channel activators have been reported to be useful for treatment of various neurological and neurodegenerative disorders. Thus far, only one metal channel activator, Retigabine, has been FDA approved. Retigabine is used as anticonvulsant for the treatment of epilepsy. Further Kv7 channel activators have been proposed for the treatment of many conditions including substance abuse and mood disorders (Vigil FA, Carver CM, Shapiro MS. Pharmacological Manipulation of K v 7 Channels as a New Therapeutic Tool forMultiple Brain Disorders. Front Physiol.2020 Jun 19;11:688. doi: 10.3389 / fphys.2020.00688). There remains a need, however, for new therapies utilizing Kv7. One solution is combining metal channel activators with other therapeutic agents to significantly improve treatment outcomes.

[0006] NDMA receptor antagonists target the NDMA receptor, a receptor which allows calcium efflux in the presence of glutamate or glycine when neurons are depolarized. NDMA receptor antagonists prevent calcium efflux and have been used as anesthetics. Recent research, primarily focused on Ketamine, has revealed an unexpected antidepressant effect. Lanicemine has been developed as an alternative antidepressant to Ketamine with reduced side effects but has not successfully treated depression as a single agent in randomized controlled trials.

[0007] Described herein are compositions and methods for combination therapies of Kv7 openers with NMDA receptor antagonists. The combination therapies have treatment capabilities greater than Kv7 openers or NMDA receptor antagonists alone, and may be particularly useful for depressive disorders. Pharmaceutical compositions combining these agents may also be useful for treatment of a pain and neurological or neurodegenerative diseases. These two agents target distinct molecular targets associated with depressive disorders, pain disorders, neurological diseases and neurodegenerative disorders. Specifically, the Kv7 channel opener reduces excitability, and NMDA receptor antagonists reduce efflux of cations such as calcium. We have found that combining Kv7 opener and an NMDA receptor antagonist will yield improved treatment outcomes as described herein. SUMMARY

[0008] The present invention is directed to combination therapies including a metal channel activator and an NMDA receptor antagonist.

[0009] In an embodiment, provided is a pharmaceutical composition including a metal channel activator and an NMDA receptor antagonist.

[0010] In another embodiment, provided is a method of treating a depressive disorder, including administering the pharmaceutical composition.

[0011] In another embodiment, provided is a method of treating a neurological or neurodegenerative disorder, including administering the pharmaceutical composition.

[0012] In another embodiment, provided is a method of treating a pain disorder, including administering the pharmaceutical composition. DETAILED DESCRIPTION

[0013] The following detailed description is provided to aid those skilled in the art in practicing the present invention. Exemplary embodiments will hereinafter be described in detail. However, these embodiments are only exemplary, and the present disclosure is not limited thereto but rather is defined by the scope of the appended claims. Those of ordinary skill in the art may make modifications and variations in the embodiments described herein without departing from the spirit or scope of the present disclosure.

[0014] Accordingly, the embodiments are merely described below, by referring to structures and schemes, to explain aspects of the present description. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed 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 and do not modify the individual elements of the list.

[0015] It will 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. Thus, a first element, component, region, layer, or section discussed below could be termed a second element, component, region, layer, or section without departing from the teachings of the present embodiments.

[0016] It is understood that the terms "comprises" and / or "comprising," or "includes" and / or "including" when used in this specification, 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.

[0017] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosurebelongs. The terminology used in the description is for describing particular embodiments only and is not intended to be limiting. It will be further understood that the terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.

[0018] As used in this application, except as otherwise expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout the application. In instances where a term is not specifically defined herein, that term is given an art-recognized meaning by those of ordinary skill applying that term in context to its use in describing the present invention.

[0019] The articles "a" and "an" refer to one or to more than one (i.e., to at least one) of the grammatical object of the article unless the context clearly indicates otherwise. By way of example, "an element" means one element or more than one element.

[0020] As used herein, when specific definition is not otherwise provided, the term "substituted" refers to a group substituted with deuterium, a halogen (-F, -Cl, -Br, -I), a hydroxy group (-OH), an amino group (-NH2), a carboxyl group (-CO2H), a substituted or unsubstituted C1-C10 amine group, a nitro group (-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 a trifluoromethyl group (-CF3) and the like, or a cyano group (-CN) instead of at least one hydrogen of a substituting group or compound.

[0021] Additional aspects will be set forth in part in the description which follows and, in part, will be apparent from the description.

[0022] As used herein, “modulator”, “modulators”, and “modulating”, when describing compounds, describe compounds that may enact their effect through a number 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 relocalization of a protein, inducing degradation of a protein, inducing stabilization of a protein, causing a conformational change in a protein, decreasing the activation threshold for a protein, increasing the activation threshold for a protein, altering posttranslational modifications for a protein, reducing the transcription of a gene, increasing the transcription of a gene, reducing the translation of an mRNA transcript, increasing the translation of an mRNA transcript,disrupting an interaction between two proteins, and stabilizing an interaction between two proteins; wherein the protein may be the target of modulation or an intermediary protein which is associated with modulation of the target protein. Modulators of the targets described herein (i.e., Kv7 and NMDA receptor) may each or both be small molecule compounds, proteins, antibody fragments or antibodies, or any other construct effecting modulation. It should be appreciated that an NMDA receptor antagonist is a type of modulator of the NMDA receptor.

[0023] As used herein, “NMDA receptor antagonist” or alternatively “NMDA modulator” means any compound (small molecule, peptide, etc.) effecting modulation or desired change in biological activity of the NMDA receptor. In various embodiments, NMDA receptor antagonists may target particular portions of an NMDA receptor, such as GluN1 (alternatively NR1) or GluN2 (alternatively NR2) subunits, or additionally or alternatively GluN3 subunits. In an embodiment, NMDA receptor antagonist target GluN1 subunits, in some cases selectively. In an embodiment, NMDA receptor antagonists target one or more GluN2 subtypes GluN2A, GluN2B, GluN2C, and / or GluN2D, in some cases selectively. In some embodiments, NMDA receptor antagonists may target one or more GluN3 subtypes GluN3A, GluN3B, and / or GluN3C, in some cases selectively. In some embodiments, NMDA receptor antagonists may target an allosteric site. In some embodiments, NMDA receptor antagonists may include partial agonists which exert dual (agonist / antagonist) effects on NMDA receptors. In certain embodiments, NMDA receptor antagonists may include agents which have a target other than the NMDA receptor which result in an NMDA receptor antagonist-like physiologic effect.

[0024] As used herein, “neurological disease” refers to a disease or disorder which affects the brain and / or nerves found elsewhere in the body. Such neurologic diseases may include: Absence of the 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 Hemiplegia, Alzheimer's Disease, Amyotrophic Lateral Sclerosis (ALS), Anencephaly, Angelman Syndrome, Antiphospholipid Syndrome, Aphasia, Apraxia, Arachnoid Cysts, Arachnoiditis, Arteriovenous Malformation, Asperger Syndrome, Ataxia Telangiectasia, Ataxias and Cerebellar or Spinocerebellar Degeneration, Atrial Fibrillation and Stroke, Attention Deficit-Hyperactivity Disorder, Autism Spectrum Disorder, Back Pain, Barth Syndrome, Batten Disease, Behcet's Disease, Bell's Palsy, Benign Essential Blepharospasm, Binswanger's Disease, Brachial Plexus Injuries, Brain and Spinal Tumors,Brown-Sequard Syndrome, CADASIL, Canavan Disease, Carpal Tunnel Syndrome, Central Cord Syndrome, Central Pain Syndrome, Central Pontine Myelinolysis, Cephalic Disorders, Cerebellar Degeneration, Cerebellar Hypoplasia, Cerebral Aneurysms, Cerebral Arteriosclerosis, Cerebral Atrophy, Cerebral Cavernous Malformation, Cerebral Hypoxia, Cerebral Palsy, Cerebro-Oculo-Facio-Skeletal Syndrome (COFS), Charcot-Marie-Tooth Disease, Chiari Malformation, Chorea, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Chronic Pain, Coffin Lowry Syndrome, Colpocephaly, Coma, Complex Regional Pain Syndrome, Congenital Myasthenia, Congenital Myopathy, Corticobasal Degeneration, Craniosynostosis, Creutzfeldt-Jakob Disease, Cushing's Syndrome, Dandy-Walker Syndrome, Deep Brain Stimulation for Movement Disorders, Dementia, Dementia With Lewy Bodies, Dermatomyositis, Developmental Dyspraxia, Diabetic Neuropathy, Dravet Syndrome, Dysautonomia, Dysgraphia, Dyslexia, Dyssynergia Cerebellaris Myoclonica, Dystonia, Empty Sella Syndrome, Encephalitis Lethargica, Encephaloceles, Encephalopathy, Epilepsy, Erb-Duchenne and Dejerine-Klumpke Palsies, Essential Tremor, Fabry Disease, Fahr's Syndrome, Familial Periodic Paralyses, Farber's Disease, Febrile Seizures, Fibromuscular Dysplasia, Foot Drop, Friedreich Ataxia, Frontotemporal Dementia, Functional Neurologic Disorder, Gaucher Disease, Generalized Gangliosidoses, Gerstmann's Syndrome, Gerstmann-Straussler-Scheinker Disease, Giant Axonal Neuropathy, Glossopharyngeal Neuralgia, Guillain-Barré Syndrome, Headache, Hemicrania Continua, Hemifacial Spasm, Hereditary Neuropathies, Hereditary Spastic Paraplegia, Herpes Zoster Oticus, Holmes-Adie Syndrome, Holoprosencephaly, Huntington's Disease, Hydranencephaly, Hydrocephalus, Hydromyelia, Hypersomnia, Hypertonia, Hypotonia, Inclusion Body Myositis, Incontinentia Pigmenti, Infantile Neuroaxonal Dystrophy, Infantile Refsum Disease, Infantile Spasms, Inflammatory Myopathies, 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, Lennox-Gastaut Syndrome, Lesch-Nyhan Syndrome, Leukodystrophy, Lipid Storage Diseases, Lipoid Proteinosis, Lissencephaly, Locked-In Syndrome, Machado-Joseph Disease and Spinocerebellar Ataxia, Megalencephaly, Melkersson-Rosenthal Syndrome, Meningitis and Encephalitis, Menkes Disease, Meralgia Paresthetica, Metachromatic Leukodystrophy, Microcephaly, Migraine, Miller Fisher Syndrome, Mitochondrial Myopathies, Moebius Syndrome, Monomelic Amyotrophy, Motor Neuron Diseases, Moyamoya Disease, Mucolipidoses,Mucopolysaccharidoses, 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 Congenita, Narcolepsy, Neuroacanthocytosis, Neurodegeneration with Brain Iron Accumulation, Neurofibromatosis, Neuroleptic Malignant 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, Paresthesia, Parkinson's Disease, Paroxysmal Choreoathetosis, Paroxysmal Hemicrania, Parry-Romberg Syndrome, Pelizaeus-Merzbacher Disease, Peripheral Neuropathy, Periventricular Leukomalacia, Pervasive Developmental Disorders, Pinched Nerve, Piriformis Syndrome, Pituitary Tumors, Polymyositis, Pompe Disease, Porencephaly, Post-Polio Syndrome, Postural Tachycardia Syndrome, Primary Lateral Sclerosis, Progressive Multifocal Leukoencephalopathy, Progressive Supranuclear Palsy, Prosopagnosia, Pseudotumor Cerebri, Rasmussen's Encephalitis, Refsum Disease, Repetitive Motion Disorders, Restless Legs Syndrome, Rett Syndrome, Reye's Syndrome, Sandhoff Disease, Schilder's Disease, Schizencephaly, Septo-Optic Dysplasia, Shaken Baby Syndrome, Shingles, Sjögren's 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, SUNCT Headache, Swallowing Disorders, Sydenham Chorea, Syncope, Syringomyelia, Tabes Dorsalis, Tardive Dyskinesia, Tarlov Cysts, Tay-Sachs Disease, Tethered Spinal Cord Syndrome, Thoracic Outlet Syndrome, Thyrotoxic Myopathy, Todd's Paralysis, Tourette Syndrome, Transient Ischemic Attack, Transmissible Spongiform Encephalopathies, Transverse Myelitis, Traumatic Brain Injury, Tremor, Trigeminal Neuralgia, Tropical Spastic Paraparesis, Troyer Syndrome, Tuberous Sclerosis, 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.

[0025] As used herein, the term “metal channel activator” is construed to include both metal channel activator and pharmaceutically acceptable salt thereof.

[0026] As used herein, the term “NMDA receptor antagonist” or “NMDA modulator” is construed to include both NMDA receptor antagonist and pharmaceutically acceptable salt thereof.

[0027] As used herein, the term “AUC” is the definite integral of the concentration of a drug in blood, cerebrospinal fluid, target organ, or any other physiologically relevant site after a dose is given as a function of time. AUC in this context is used to measure the total exposure to the drug across time. AUC can be evaluated over a definite time interval or estimated based on the integral drug concentrations measured over a time interval extrapolated to infinite time.

[0028] As used herein, the term “Cmax” is the highest concentration of a drug in the blood, cerebrospinal fluid, target organ, or any other physiologically relevant site after a dose is given.

[0029] As used herein, the term “Tmax” is the time taken after administration for a drug to reach its highest concentration in the blood, cerebrospinal fluid, target organ, or any other physiologically relevant site after a dose is given.

[0030] As used herein, the term “proteinopathies” refers to diseases characterized by an 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 Lewy Body Dementia.

[0031] Additional aspects will be set forth in part of the description which follows and, in part, will be apparent from the description.

[0032] In the formulas set forth below, it is set out with substituents and definitions, and it should be clear to the reader that substituents and definitions are numbered (e.g., R1, R2, Y, etc.) and are intended to apply within a given formula. Numberings that are repeated across formulas are intentional and should be each read within the context of each particular formula. METAL CHANNEL ACTIVATOR

[0033] Examples of metal channel activators including Kv7 channel activators are disclosed in Formulas 1 – 171, the “Further embodiments” section, and in the corresponding referenced applications.Formula 1

[0034] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 1. Such compounds are described in US Patent No 9,481,653, issued November 1, 2016, and corresponding to US Application No. 14 / 853,815 filed September 14, 2015; and US Publication No 20210188782A1, published June 24, 2021, and corresponding to US Application No.17 / 127,231 filed December 18, 2020; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 1, these references incorporated by reference herein control.

[0035] In an embodiment, the Kv7 channel activator is a compound according to formula 1: Formula 1, wherein D is optionally substituted C3-6carbocyclyl, optionally substituted C2-5heterocyclyl, isopropyl, or t-butyl; Bz is optionally substituted benzoimidazol-1,2-diyl; A is C1-8alkyl; X is F; 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.

[0036] In further embodiments, D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t- butyl.

[0037] In further embodiments, D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t- 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.

[0038] In another embodiment, the Kv7 channel activator is a compound according to formula 1 wherein, D is optionally substituted C3-6carbocyclyl, optionally substituted C2-5heterocyclyl, isopropyl, or t-butyl; Bz is optionally substituted benzoimidazol-1,2-diyl; A is C1-8alkyl; X is H, F, CF3, optionally substituted phenyl, or optionally substituted pyridinyl; 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.

[0039] In further embodiments, D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t- butyl.

[0040] In further embodiments, each substituent of D, X, 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.

[0041] In further embodiments, R1is H, Cl, Br, CN, OCH3, CF3, —CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl.

[0042] In further embodiments, X is optionally substituted phenyl.

[0043] In further embodiments, X is CF3.

[0044] In further embodiments, X is optionally substituted pyridinyl.

[0045] In further embodiments, X is H.

[0046] In further embodiments, Y is H.

[0047] In further embodiments, Y is OH.

[0048] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:Formula 2

[0049] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 2. Such compounds are described in US Patent No.9,481,653 issued November 1, 2016 and corresponding to US Application No. US14 / 853,815 filed September 14, 2015; US Patent No.9,914,708, issued March 13, 2018 and corresponding to US Application No.15 / 339,590 filed October, 31; US patent No 10,385,025, issued August 20, 2019 and corresponding to US Application No.15 / 879,792 filed January 25, 2018; US Patent No.10,906,877 issued on February 2, 2021 and corresponding to US Application No.16 / 460,449 filed July 2, 2019; US Patent No. 10,851,067 issued on December 1, 2020 and corresponding to US Application No. 16 / 358,642 filed March 19, 2019; US Patent No.11,261,162 issued on March 1, 2022 and corresponding to US Application No.17 / 077,068 filed October 22, 2020; US Publication No. 20210188782A1, published June 24, 2021 and corresponding to US Application No. 17 / 127,231 filed December 18, 2020; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 2, these references incorporated by reference herein control.

[0050] In an embodiment, the Kv7 channel activator is a compound according to formula 2:Formula 2, wherein D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t-butyl; A is C2-8alkyl; X is H, F, CF3optionally substituted phenyl, or optionally substituted pyridinyl; 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; R1is F, Cl, Br, CN, OCH3, CHF2, CF3, C1-4—CO2-alkyl, C1-4alkyl, —CH2CO2H, — CH2CO2CH2CH3or —CH2CON(CH3)2, or C1-5hydroxyalkyl; and R2, R3, and R4are independently H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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.

[0051] In further embodiments, Y is H, F, CF3, OH, C1-5O-alkyl, C0-6alkylamino, optionally substituted tetrahydropyranyl, or C0-6fluoroalkylamino.

[0052] In further embodiments R1is 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.

[0053] In further embodiments, R2is H, F, —CH2OH, —CO2Me, or —C(CH3)2OH.

[0054] In further embodiments, R3is H.

[0055] In further embodiments, R4is H, —CH3, or —CF3.

[0056] In further embodiments, R1is Cl, Br, CN, OCH3, CF3, —CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl.

[0057] In further embodiments, X is optionally substituted phenyl.

[0058] In further embodiments, X is CF3.

[0059] In further embodiments, X is optionally substituted pyridinyl.

[0060] In further embodiments, X is H.

[0061] In further embodiments, Y is H.

[0062] In further embodiments, Y is OH.

[0063] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0064] In further embodiments, the Kv7 channel activator is a compound according to formula 2 wherein, D is optionally substituted cyclobutyl, or t-butyl; A is C2-8alkyl; X is H, CF3, or optionally substituted phenyl; Y is H or OH; R1is CN or C1-4hydroxyalkyl; and R2, R3, and R4are independently H, or F.

[0065] In further embodiments, R1is CN, —C(CH3)2OH, or —CH2C(CH3)2OH.

[0066] In further embodiments, R2is F.

[0067] In further embodiments, R3is H.

[0068] In further embodiments, R4is H.

[0069] In further embodiments, R1is CN.

[0070] In further embodiments, R1is C1-4hydroxyalkyl.

[0071] In further embodiments, X is optionally substituted phenyl.

[0072] In further embodiments, X is CF3.

[0073] In further embodiments, X is H.

[0074] In further embodiments, Y is H.

[0075] In further embodiments, Y is OH.

[0076] In further embodiments, the Kv7 channel activator is a compound according to formula 2 wherein, D is cyclobutyl; A is C1-8alkyl; X is CF3; Y is H; R1is H, Cl, Br, CN, OCH3, CF3, —CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, —CH2OH, — CO2Me, or —C(CH3)2OH; R3is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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 R4is H, —CH3, or —CF3; or D is optionally substituted cyclobutyl; A is C1-8alkyl; X is CF3; Y is H; R1is H, Cl, Br, CN, OCH3, CF3, —CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, —CH2OH, —CO2Me, or —C(CH3)2OH; R3is H; and R4is H, —CH3, or —CF3;or D is t-butyl; A is C1-8alkyl; X is H; Y is H; R1is Cl, Br, CN, OCH3, CF3, — CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, —CH2OH, —CO2Me, or — C(CH3)2OH; R3is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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 R4is H, —CH3, or —CF3; or D is t-butyl; A is C1-8alkyl; X is CF3; Y is H; R1is H, Cl, Br, CN, OCH3, CF3, — CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, —CH2OH, —CO2Me, or — C(CH3)2OH; R3is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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 R4is H, —CH3, or —CF3; or D is cyclobutyl; A is C1-8alkyl; X is H; Y is methyl(2,2,2-trifluoroethyl)amino; R1is H, Cl, Br, CN, OCH3, CF3, —CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, — CH2OH, —CO2Me, or —C(CH3)2OH; R3is H; and R4is H, —CH3, or —CF3; orD is cyclobutyl; A is C1-8alkyl; X is CF3; Y is dimethylamino; R1is H, Cl, Br, CN, OCH3, CF3, —CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, —CH2OH, — CO2Me, or —C(CH3)2OH; R3is H; and R4is H, —CH3, or —CF3; or D is optionally substituted cyclobutyl, optionally substituted phenyl, or optionally substituted C2-5alkyl, wherein the optional substituents are selected from —CH3and F; A is C1alkyl; X is substituted cyclobutyl, wherein the substituent is F;Y is H; R1is selected from H, C3hydroxyalkyl, CN, F, or Cl; R2is selected from H, CN, F, Br, or —OCF3; R3is selected from H, F, or —OCH3; R4is H or F; and wherein when X is substituted with 2 fluorine atoms, the fluorine atoms are not geminal; or a pharmaceutically acceptable salt thereof;

[0077] In an embodiment, the Kv7 channel activator is a compound according to formula 2. Wherein, R1, R2, R3, and R4are independently H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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.

[0078] In further embodiments, Y is H, F, CF3, OH, C1-5O-alkyl, C0-6alkylamino, optionally substituted tetrahydropyranyl, or C0-6fluoroalkylamino.

[0079] In further embodiments, R1is 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.

[0080] In further embodiments, R2is H, F, —CH2OH, —CO2Me, or —C(CH3)2OH.

[0081] In further embodiments, R3is H.

[0082] In further embodiments, R4is H, —CH3, or —CF3.

[0083] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:or a pharmaceutically acceptable salt thereof.

[0084] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:or a pharmaceutically acceptable salt thereof.

[0085] In further embodiments the Kv7 channel activator is a compound selected from the group consisting of:or a pharmaceutically acceptable salt thereof.

[0086] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:or a pharmaceutically acceptable salt thereof.

[0087] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0088] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0089] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0090] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0091] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0092] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0093] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0094] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0095] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0096] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0097] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:or a pharmaceutically acceptable salt thereof.

[0098] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:or a pharmaceutically acceptable salt thereof.

[0099] In further embodiments, the Kv7 channel activator is a compound selected from the group consisting of:

[0100] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0101] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0102] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0103] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0104] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0105] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0106] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0107] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0108] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0109] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0110] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0111] In further embodiments, the compound is:or a pharmaceutically acceptable salt thereof.

[0112] In an embodiment of Formula 2, D is optionally substituted cyclobutyl, or t-butyl; A is C2-8alkyl, X is H, CF3, or optionally substituted phenyl, Y is H or OH, R1is CN or C1-4hydroxyalkyl; and R2, R3, and R4are independently H, or F. In a further embodiment, R1is CN, -C(CH3)2OH, or -CH2C(CH3)2OH. In a further embodiment, R2is F. In a further embodiment, R3is H. In a further embodiment, R4is H. In a further embodiment, R1is CN. In a further embodiment, R1is C1-4hydroxyalkyl. In a further embodiment, X is optionallysubstituted phenyl. In a further embodiment, X is CF3. In a further embodiment, X is H. In a further embodiment, Y is H. In a further embodiment, Y is OH.

[0113] In an embodiment of Formula 2, D is cyclobutyl; A is C1-8alkyl, X is CF3, Y is H, R1is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, - CH2OH, -CO2Me, or -C(CH3)2OH; R3is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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 R4is H, -CH3, or -CF3.

[0114] In an embodiment of Formula 2, D is optionally substituted cyclobutyl, A is C1-8alkyl, X is CH3, Y is H, R1is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, -CH2OH, -CO2Me, or -C(CH3)2OH; R3is H; and R4is H, -CH3, or - CF3.

[0115] In an embodiment of Formula 2, D is t-butyl; A is C1-8alkyl; X is H; Y is H; R1is Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, -CH2OH, - CO2Me, or -C(CH3)2OH; R3is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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 R4is H, -CH3, or -CF3.

[0116] In an embodiment of Formula 2, D is t-butyl; A is C1-8alkyl; X is CF3; Y is H; R1is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, - CH2OH, -CO2Me, or -C(CH3)2OH; R3is H, F, Cl, Br, I, or a substituent having a molecular weight of 15 Da 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 R4is H, CH3, or CF3.

[0117] In an embodiment of Formula 2, D is cyclobutyl; A is C1-8alkyl; X is H; Y is methyl(2,2,2-trifluoroethyl)amino; R1is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C1-4alkyl, or C1-4hydroxyalkyl; R2is H, F, -CH2OH, -CO2Me, or -CH(CH3)2OH; R3is H; and R4is H, - CH3, or -CF3.

[0118] In an embodiment of Formula 2, D is optionally substituted cyclobutyl, optionally substituted phenyl, or optionally substituted C2-5alkyl, wherein the optional substituents are selected from -CH3and F; A is C1alkyl, X is substituted cyclobutyl, wherein the substituent is F; Y is H; R1is selected from H, C3hydroxyalkyl, CN, F, or Cl; R2is selected from H, CN, F, Br, or -OCF3; R3is selected from H, F, or -OCH3; R4is H or F; and wherein when X is substituted with 2 fluorine atoms, the fluorine atoms are not geminal; or a pharmaceutically acceptable salt thereof.Formula 3 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 3. Such compounds are described in US Patent No. 8,293,911 issued on October 23, 2012 and corresponding to US Application No.11 / 894,877 filed August 22, 2007; which is incorporated by reference in its entirety herein. In the case of any conflict of terminology in the context of Formula 3, this reference incorporated by reference herein controls.

[0119] In an embodiment, the Kv7 channel activator is a compound according to formula 3: Formula 3, wherein, R1and R2, vary independently, and are selected from the group consisting of H, CN, halogen, CH2CN, OH, CH2F, CHF2, CF3, CF2CF3, C1-C6alkyl, C(═O)C1-C6alkyl; NH—C1- C6alkyl; N(C1-C6alkyl)-C1-C6alkyl, NHC(═O)C1-C6alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH2, C(═O)NH—C1-C6alkyl, SO2NH2, NHSO2—C1-C6alkyl; C(═O)OC1-C6alkyl, OC(═O)C1-C6alkyl, OC1-C6alkyl, SC1-C6alkyl, C3-C6cycloalkyl, (CH2)mC3-C6cycloalkyl, C3-C6cycloalkenyl, (CH2)mC3-C6cycloalkenyl, C2-C6alkenyl, C2-C6alkynyl, Ar, (CH2)mthienyl, (CH2)mimidazolyl, (CH2)mpyrazyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, and (CH2)mpyrimidyl, Wherein m=zero, 1, or 2; Ar is a 5- to 10-member mono- or bicyclic aromatic group, optionally containing 1-4 ring heteroatoms selected independently from N, O, and S; or R1and R2, together with the ring carbon atoms to which they are attached, form a 5- or 6-member fused ring; wherein said fused ring may be saturated, unsaturated, or aromatic, and said fused ring optionally contains one or two heteroatoms selected independently 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-C3alkyl and C1- C3alkyl; R3and R4vary independently, and are selected from the group consisting of H, CN, halogen, CF3, OCF3, OC1-C3alkyl, and C1-C3alkyl; X is O or S; Y is O or S; q=1 or zero; and R5is selected from the group consisting of C1-C6alkyl, (CHR6)wC3-C6cycloalkyl, (CHR6)wCH2C3-C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, CR6═CH—C3-C6cycloalkyl, CH═CR6—C3-C6cycloalkyl, (CHR6)wC5-C6cycloalkenyl, CH2(CHR6)wC5-C6cycloalkenyl,C2-C6alkenyl, C2-C6alkynyl, Ar, (CHR6)wAr, CH2(CHR6)wAr, and (CHR6)wCH2Ar, wherein w=zero, 1, 2, or 3; Ar is a 5- to 10-member mono- or bicyclic aromatic group, optionally containing 1-4 ring heteroatoms selected independently from the group consisting of N, O, and S; and R6is selected from the group consisting of H or C1-C3alkyl; where all cycloalkyl and cycloalkenyl optionally contain one or two ring heteroatoms selected independently 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 selected independently from the group consisting of C1-C3alkyl, halogen, OH, OEt, OMe, CN, CH2F, OCF3, and CF3; and wherein, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with a carbonyl group.

[0120] In further embodiments, R1and R2, vary independently, and are selected from the group consisting of H, halogen, CF3, C1-C6alkyl, C(═O)C1-C6alkyl, C(═O)OC1-C6alkyl, OC(═O)C1-C6alkyl, OC1-C6alkyl, SCH3, C3-C6cycloalkyl, (CH2)mC3-C6cycloalkyl, phenyl, pyridyl, pyrrolyl, thienyl, (CH2)mphenyl, (CH2)mpyrrolyl, and (CH2)mpyridyl; wherein said cycloalkyl groups optionally contain one or two heteroatoms selected independently from the group consisting of O, N, and S; wherein said alkyl, cycloalkyl, phenyl, pyrrolyl, and pyridyl groups are optionally substituted with one or two groups selected, independently, 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-C3alkyl and C1-C3alkyl; R3and R4vary independently, and are selected from the group consisting of H, halogen, CF3, OCF3, OC1-C3alkyl, and C1-C3alkyl; X is O or S; Y is O or S; q=1 or 0; R5is selected from the group consisting of C1-C6alkyl, (CHR6)wC3-C6cycloalkyl, (CHR6)wCH2C3-C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, CR6═CH—C3-C6cycloalkyl, CH═CR6—C3-C6cycloalkyl, (CHR6)wC5-C6cycloalkenyl, CH2(CHR6)wC5-C6cycloalkenyl, C2-C6alkenyl, C2-C6alkynyl, Ar, (CHR6)wAr, CH2(CHR6)wAr, and (CHR7)wCH2Ar; wherein w=0-3; Ar is selected from the group consisting of phenyl, pyrimidyl, or pyridyl, and a 5- member heteroaromatic ring; wherein said heteroaromatic ring contains 1 or 2 ring heteroatoms selected independently from the group consisting of N, O, and S; and R6is selected from the group consisting of H and methyl; wherein all cycloalkyl and cycloalkenyl groups in R5optionally contain one or two ring heteroatoms selected independently 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 selected independently from the group consisting of C1-C3alkyl, halogen, OEt, OMe, and trifluoromethyl.

[0121] In further embodiments, R1and R2, vary independently, and are selected from the group consisting of H, halogen, CF3, C1-C6alkyl, C(═O)C1-C6alkyl, C(═O)OC1-C6alkyl, OC(═O)C1-C6alkyl, OC1-C6alkyl, SCH3, (CH2)mcyclopropyl, (CH2)mcyclobutyl, (CH2)mcyclopentyl, (CH2)mcyclohexyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, and (CH2)mpyrimidyl; wherein said cyclopentyl and said cyclohexyl groups optionally contain one or two ring heteroatoms selected independently from the group consisting of O, N, and S; wherein said alkyl, cycloalkyl, phenyl, pyrrolyl, and pyridyl groups are optionally substituted with one or two groups selected, independently, 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-C3alkyl; R3and R4vary independently, and are selected from the group consisting of H, halogen, CF3, OCF3, OC1-C3alkyl, and C1-C3alkyl; X is O or S; Y is O; q=1 or 0; R5is selected from the group consisting of C1-C6alkyl, (CHR6)wC3-C6cycloalkyl, (CHR6)wCH2C3- C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, CR6═CH—C3-C6cycloalkyl, CH═CR6—C3- C6cycloalkyl, (CHR6)wC5-C6cycloalkenyl, CH2(CHR6)wC5-C6cycloalkenyl, C2-C6alkenyl, C2-C6alkynyl, Ar, (CHR6)wAr, CH2(CHR6)wAr, and (CHR6)wCH2Ar; wherein w=0-3, Ar is selected from the group consisting of phenyl, pyridyl, and a 5-member heteroaromatic ring, wherein said heteroaromatic ring contains 1 or 2 ring heteroatoms selected independently from the group consisting of N, O, and S; R6is H or methyl; wherein all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms selected independently 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 selected independently from the group consisting of C1-C3alkyl, halogen, OMe, OEt, and CF3.

[0122] In further embodiments, R1and R2, vary independently, and are selected from the group consisting of H, halogen, CF3, OC1-C3alkyl, C1-C6alkyl, C(═O)OC1-C3alkyl, OC(═O)C1-C3alkyl, and C(═O)C1-C3alkyl; R′ is selected from the group consisting of H, F, CH3, and ethyl; R3and R4vary independently, and are selected from the group consisting of H, F, Cl, CF3, OCF3, OC1-C3alkyl, and C1-C3alkyl; and R5is C1-C6alkyl, (CHR6)wC3- C6cycloalkyl, (CHR6)wCH2C3-C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, or (CHR6)wAr, CH2(CHR6)wAr, or (CHR6)wCH2Ar.

[0123] In further embodiments, R2is H or F; R′ is H; R3is selected from the group consisting of H, CH3, OCH3, CF3, OCF3, and Cl; R4is selected from the group consisting of CH3, OCH3, CF3, OCF3, and Cl; and R5is C3-C6alkyl or (CH2)wC3-C6cycloalkyl.

[0124] In further embodiments, R1is halogen or CF3; R2is H or F; R′ is H; R3and R4vary independently, and are selected from the group consisting of H, CH3, OCH3, CF3, OCF3, or Cl; and R5is selected from the group consisting of C1-C6alkyl, (CHR6)wC3-C6cycloalkyl, (CHR6)wCH2C3-C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, CR6═CH—C3-C6cycloalkyl, CH═CR6—C3-C6cycloalkyl, (CHR6)wC5-C6cycloalkenyl, CH2(CHR6)wC5-C6cycloalkenyl, C2-C6alkenyl, C2-C6alkynyl, Ar, (CHR6)wAr, CH2(CHR6)wAr, and (CHR6)wCH2Ar.

[0125] In further embodiments, R1is halogen or CF3; R2is H or F; R′ is H; R3and R4vary independently, and are selected from the group consisting of H, CH3, OCH3, CF3, OCF3, or Cl; and R5is selected from the group consisting of C1-C6alkyl, (CHR6)wC3-C6cycloalkyl, (CHR6)wCH2C3-C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, CR6═CH—C3-C6cycloalkyl, CH═CR6—C3-C6cycloalkyl, (CHR6)wC5-C6cycloalkenyl, CH2(CHR6)wC5-C6cycloalkenyl, C2-C6alkenyl, C2-C6alkynyl, Ar, (CHR6)wAr, CH2(CHR6)wAr, and (CHR6)wCH2Ar. Formula 4

[0126] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 4. Such compounds are described in US Patent No.8,293,911 issued on October 23, 2012 and corresponding to US Application No. 11 / 894,877; which is incorporated by reference in its entirety herein. In the case of any conflict of terminology in the context of Formula 4, this reference incorporated by reference herein controls.

[0127] In an embodiment, the Kv7 channel activator is a compound according to formula 4: Formula 4, wherein, R1is selected from the group consisting of H, halogen, CN, CH2CN, CF3, C1- C6alkyl, OCH3, (C═O)OCH3, O(C═O)CH3, OCF3, (CH2)mC3-C6cycloalkyl, phenyl, andpyridyl; R2is selected from the group consisting of H, F, OCH3, CH3, and CF3; R3and R4vary independently, and are selected from the group consisting of H, F, Cl, CF3, OCF3, OC1-C3alkyl, or C1-C3alkyl; and R5is selected from the group consisting of C1-C6alkyl, (CHR6)wC3-C6cycloalkyl, (CHR6)wCH2C3-C6cycloalkyl, CH2(CHR6)wC3-C6cycloalkyl, CR6═CH—C3-C6cycloalkyl, CH═CR6—C3-C6cycloalkyl, (CHR6)wC5-C6cycloalkenyl, CH2(CHR6)wC5-C6cycloalkenyl, C2-C6alkenyl, C2-C6alkynyl, Ar, (CHR6)wAr, CH2(CHR6)wAr, and (CHR6)wCH2Ar, wherein w=0-3; Ar is phenyl, furyl, pyrrolyl, oxazolyl, thiazolyl, thienyl, or pyridyl; and R6is C1-C3alkyl; 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 selected independently from the group consisting of C1-C3alkyl, halogen, OCH3, OCH2CH3, CN, and CF3.

[0128] In other embodiments, R1is selected from the group consisting of H, F, Cl, Br, CF3, C1-C6alkyl, OCH3, CH2OCH3, CH2CH2OCH3, CH2OCH2CH3, 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 R5is selected from the group consisting of C1-C6alkyl, CH2C3-C6cycloalkyl, CH2CH2C3- C6cycloalkyl, CH═CH—C3-C6cycloalkyl, CH═CH—C5-C6cycloalkenyl, CH2C5- C6cycloalkenyl, CH2CH2C5-C6cycloalkenyl, C2-C6alkenyl, 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 selected independently from the group consisting of CH3, halogen, OCH3, OCH2CH3, CN, and CF3.

[0129] In other embodiments, R1is selected from the group consisting of H, F, Cl, Br, CF3, C1-C6alkyl, OCH3, CH2OCH3, CH2CH2OCH3, CH2OCH2CH3, and OCH2CH3; R′ is selected from the group consisting of H, CH3, CH2CH3, or halogen; R3and R4vary independently, and are selected from the group consisting of H, F, Cl, CF3, OCF3, OCH3, and CH3; and R5is selected from the group consisting of C1-C6alkyl, CH2C3-C6cycloalkyl, CH2CH2C3- C6cycloalkyl, CH═CH—C3-C6cycloalkyl, CH═CH—C5-C6cycloalkenyl, CH2C5- C6cycloalkenyl, CH2CH2C5-C6cycloalkenyl, C2-C6alkenyl, 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 selected independently from the group consisting of CH3, halogen, OCH3,OCH2CH3, CN, and CF3. Wherein, R1is selected from the group consisting of F, CF3, Cl, CH3, CH2CH3, SCH3, OCH3, CH2OCH3, CH2OCH2CH3, OCF3, phenyl, thienyl, and H; R2is selected from the group consisting of H, F, Cl, and OCH3; R′ is selected from the group consisting of H, F, CH2CH3, and CH3; R3and R4vary independently, and are selected from the group consisting of H, Cl, CH3, CF3, OCH3, and OCF3; and R5is selected from the group consisting of C4-C6alkyl, (CH2)wAr, and (CH2)wC5-C6cycloalkyl; wherein w is 1, 2, or 3.

[0130] In other embodiments, R1is selected from the group consisting of F, CF3, Cl, CH3, OCH3, CH2OCH3, and H; R2is selected from the group consisting of H, F, CH3, and Cl; R′ is H; R3is selected from the group consisting of H, Cl, CH3, CF3, OCH3, and OCF3; R4is selected from the group consisting of Cl, OCH3, and CH3; and R5is C4-C6alkyl or 2- cyclopentyl ethyl.

[0131] In other embodiments, R3and R4are both CH3or both OCH3; and R5is C5-C6alkyl.

[0132] In other embodiments, R′ and R2are H; R3and R4are both methyl; and R5is C5- C6alkyl or (CH2)wC5-C6cycloalkyl; wherein w is 1, 2, or 3.

[0133] 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-cyclopentylpropanamide; N-(2-chloro-4-(6-fluoro-3,4- dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethylphenyl)-3,3-dimethylbutanamide; N-[2- chloro-4-(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)-6-trifluoromethyl phenyl]-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-trifluoromethyl phenyl]-3,3-dimethylbutanamide; N-[4- (6-chloro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutanamide; N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl phenyl]-3,3- dimethylbutanamide; N-[2-chloro-4-(7-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6- trifluoromethyl-phenyl]-3,3-dimethylbutanamide; N-[4-(7-fluoro-3,4-dihydro-1H- isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutanamide; N-[2-chloro-4-(6-fluoro- 3,4-dihydro-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-dimethyl butanamide; 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-dimethyl butanamide. Formula 5 In another embodiment, the Kv7 channel activator may be selected from one of the following compounds. Such compounds are described in US Patent No.8,993,593 issued on March 31, 2015 and corresponding to US Application No.12 / 698,070 filed February 1, 2010; US Publication No. US20220265634A1, published August 25, 2022 and corresponding to US Application No.17 / 668,340 filed February 9, 2022;which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 5, these references incorporated by reference herein control.

[0134] In an embodiment, the Kv7 channel activator is a compound according to formula 5: Formula 5 ,optionally wherein the compound is substituted at any position. Formula 6

[0135] In another embodiment, the Kv7 channel activator may be the following compound (ezogabine, also known as retigabine) or a pharmaceutically acceptable salt thereof. Ezogabine is a compound according to formula 6: In the case of any conflict of terminology in the context of Formula 6, these references incorporated by reference herein control. Formula 6, or, optionally, wherein the compound is substituted at any position. Formula 7 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 7. Such compounds are described in US Patent No. 10,526,328 issued on January 7, 2020 and corresponding to US Application No.16 / 124,853 filed September 7, 2018; US Patent No.10,106,536 issued on October 23, 2018 and corresponding to US Application No.15 / 591,844 filed on May 10, 2017; US Patent No. 9,650,376 issued on May 16, 2017, and corresponding to US Application No.14 / 776,271 filed March 17, 2014;; US Publication No. US20220060208A1, published February 24, 2022 and corresponding to US Application No.17 / 277,145 filed January 14, 2019; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 7, these references incorporated by reference herein control.

[0136] In an embodiment, the Kv7 channel activator is a compound according to formula 7: Formula 7,wherein, L is CH2; R1is optionally substituted cyclic C3H5, wherein the optional substituent of R1is CF3; R2is optionally substituted cyclobutyl; R3is optionally substituted C3alkyl, wherein the optional substituent of R3is OH; R4is H; and R5is H; or wherein, L is CH2; R1is optionally substituted C2alkyl, wherein the optional substituents of R1are independently CF3or CH3; R2is optionally substituted cyclobutyl; R3is optionally substituted C3alkyl, wherein the optional substituent of R3is OH; R4is H; and R5is H; or wherein, wherein L is CH2, CF2, CHCH3, CH2CH2, C3H6, CH2O, C2H4O, or C3H6O with the O of CH2O, C2H4O, or C3H6O bonded with R1; wherein R1is optionally substituted C1-2alkyl, optionally substituted C5-10cycloalkyl, optionally substituted C1-12—O-alkyl, optionally substituted C6-10aryl, optionally substituted C6-10—O-aryl, or optionally substituted C2-9heterocyclyl, wherein the optional substituents of R1are independently RA, F, Cl, CN, ORA, CF3, NRARB, CORA, CO2RA, OCORA, NRACORB, CONRARB, wherein RAand RBare independently H or C1-12alkyl; wherein R2is optionally substituted C2-4acyclic alkyl, optionally substituted cyclobutyl, optionally substituted C6-10aryl, or optionally substituted C2-9heterocyclyl, wherein the optional substituents of R2are independently F, Cl, Br, I, CN, C1-6alkyl, C1-6—O-alkyl, C1-6alkylamine, C1-6aminoalkyl, C1-6aminoacyl, C1-6alkylthio, or C1-6alkylsulfonyl; wherein R3, R4, and R5are independently H, F, Cl, Br, I, CN, optionally substituted C1-12alkyl, optionally substituted C1-12—O-alkyl, optionally substituted C2-9heterocyclyl, optionally substituted C6-10aryl, optionally substituted C2-9—O-heterocyclyl, optionally substituted C6-10O-aryl, optionally substituted C1-12acylamino, optionally substituted C1-12aminoacyl, or optionally substituted C1-12aminoalkyl, wherein the optional substituents of R3, R4, or R5are independently F, Cl, Br, I, CN, C1-6alkyl, C1-6—O-alkyl, C1-6alkylamine, C1-6aminoalkyl, C1-6aminoacyl, C1-6acylamino, C1-6alkylthio, or C1-6alkylsulfonyl.

[0137] In further embodiments, R2is optionally substituted C4H9, optionally substituted cyclobutyl, optionally substituted C6-10aryl, or optionally substituted C2-9heterocyclyl.

[0138] In further embodiments, R2is optionally substituted C4H9, or optionally substituted cyclobutyl.

[0139] In further embodiments, R2is optionally substituted phenyl, or optionally substituted C2-9heterocyclyl.

[0140] In further embodiments, R1is optionally substituted phenyl.

[0141] In further embodiments, R1is optionally substituted phenyl.

[0142] In further embodiments, R1is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0143] In further embodiments, R1is C2-4—O-alkyl.

[0144] In further embodiments, R1is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl.

[0145] In further embodiments, R1is selected from the group consisting of:

[0146] In further embodiments, R2is selected from the group consisting of:

[0147] In further embodiments, R3is CF3, Cl, CN, OCH3, or H.

[0148] In further embodiments, R1is selected from the group consisting of:

[0149] In further embodiments, R4is CH3, CF3, Cl, or H.

[0150] In further embodiments, R2is selected from the group consisting of:

[0151] In further embodiments, the Kv7 channel activator is selected from the group consisting of:

[0152] In further embodiments, the Kv7 channel activator is selected from the group consisting of:Formula 8 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 8. Such compounds are described in US Patent No. 9,650,376, published on February 4, 2014 and corresponding to US Application No. 14 / 776,271 filed March 17, 2014; which is incorporated by reference in its entirety herein. In the case of any conflict of terminology in the context of Formula 8, this reference incorporated by reference herein controls.

[0153] In an embodiment, the Kv7 channel activator is a compound according to formula 8: Formula 8, wherein, L is CH2, CF2, CHCH3, CH2CH2, C3H6, CH2O, C2H4O, or C3H6O with the O of CH2O, C2H4O, or C3H6O bonded with R1; wherein R1is optionally substituted C1-2alkyl, optionally substituted C5-10cycloalkyl, optionally substituted C1-12—O-alkyl, optionally substituted C6-10aryl, optionally substituted C6-10—O-aryl, or optionally substituted C2-9heterocyclyl, wherein the optional substituents of R1are independently RA, F, Cl, CN, ORA, CF3, NRARB, CORA, CO2RA, OCORA, NRACORB, CONRARB, wherein RAand RBare independently H or C1-12alkyl; wherein R2is optionally substituted C2-4acyclic alkyl, optionally substituted cyclobutyl, optionally substituted C6-10aryl, or optionally substituted C2-9heterocyclyl, wherein the optional substituents of R2are independently F, Cl, Br, I, CN, C1-6alkyl, C1-6—O-alkyl, C1-6alkylamine, C1-6aminoalkyl, C1-6aminoacyl, C1-6alkylthio, or C1-6alkylsulfonyl; wherein R3, R4, and R5are independently H, F, Cl, Br, I, CN, optionally substituted C1-12alkyl, optionally substituted C1-12—O-alkyl, optionally substituted C2-9heterocyclyl, optionally substituted C6-10aryl, optionally substituted C2-9—O-heterocyclyl, optionally substituted C6-10O-aryl, optionally substituted C1-12acylamino, optionally substituted C1-12aminoacyl, or optionally substituted C1-12aminoalkyl, wherein the optional substituents of R3, R4, or R5are independently F, Cl, Br, I, CN, C1-6alkyl, C1-6—O-alkyl, C1-6alkylamine, C1-6aminoalkyl, C1-6aminoacyl, C1-6acylamino, C1-6alkylthio, or C1-6alkylsulfonyl.

[0154] In further embodiments, R2is optionally substituted C4H9, optionally substituted cyclobutyl, optionally substituted C6-10aryl, or optionally substituted C2-9heterocyclyl.

[0155] In further embodiments, R2is optionally substituted C4H9, or optionally substituted cyclobutyl.

[0156] In further embodiments, R2is optionally substituted phenyl, or optionally substituted C2-9heterocyclyl.

[0157] In further embodiments, R1is optionally substituted phenyl.

[0158] In further embodiments, R1is optionally substituted phenyl.

[0159] In further embodiments, R1is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0160] In further embodiments, R1is C2-4—O-alkyl.

[0161] In further embodiments, R1is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl.

[0162] In further embodiments, R1is selected from the group consisting of:

[0163] In further embodiments, R2is selected from the group consisting of:

[0164] In further embodiments, R3is CF3, Cl, CN, OCH3, or H.

[0165] In further embodiments, R1is selected from the group consisting of:

[0166] In further embodiments, R4is CH3, CF3, Cl, or H.

[0167] In further embodiments, R2is selected from the group consisting of:Formula 9

[0168] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 9. Such compounds are described in International Publication No. WO2021023616A1, published February 11, 2021 and corresponding to International Application No. PCT / EP2020 / 071514 filed July 30, 2020; International Publication No. WO2019161877A1, published August 29, 2019 and corresponding to International Application No. PCT / EP2018 / 054057 filed February 20, 2018; US Publication No. US20220280455A1, published September 8, 2022 and corresponding to US Application No.17 / 631,762 filed July 30, 2020; US Publication No. US20210032196A1, published February 4, 2021 and corresponding to US Application No.16 / 943,872 filed July 30, 2020; US Publication No. US20210032196A1, published February 4, 2021 and corresponding to US Application No.16 / 943,872 filed July 30, 2020;, , which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 9, these references incorporated by reference herein control.

[0169] In an embodiment, the Kv7 channel activator is a compound according to formula 9: Formula 9wherein, R1 is selected from the group consisting of C1-C6alkyl, CF3, CH2CF3, CF2CHF2, C3-C8cycloalkyl, wherein said C3-C8cycloalkyl may be substituted with 1 or 2 substituents selected from the group consisting of C1-C3alkyl, F, CHF2and CF3; and R2 is H, C1-C6alkyl or CF3; or R1 and R2 combine to form C3-C5cycloalkyl optionally substituted with 1 or 2 F, CHF2or CF3; and R3 is C1-C3alkyl or CH2O—C1-3alkyl, said C1-C3alkyl or CH2O—C1-C3is alkyl substituted with C≡N, 3 F or C3-C5cycloalkyl; R4 is selected from the group consisting of OCF3, or OCHF2

[0170] In further embodiments, R4 is OCF3or OCHF2.

[0171] In further embodiments, R3 is selected from the group consisting of CH2—O—CF3, CH2—O— cyclopropyl, CH2—C≡N.

[0172] In further embodiments R1 is C3-C4cycloalkyl optionally substituted with 1 or 2 C1- C3alkyl, F, CHF2or CF3.

[0173] In further embodiments, R1 and R2 combine to form cyclobutyl optionally substituted with 1 or 2 F and R4 is OCF3or OCHF2.

[0174] In further embodiments, the Kv7 channel activator is selected from the group consisting of: (S)—N—((R)-2-cyclopropoxy-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; (S)—N—((S)-3-cyano-1-(3-(trifluoromethoxy)phenyl) propyl)-3- hydroxy-4,4-dimethylpentanamide; (R)—N-(2-cyclopropoxy-1-(3-(trifluoromethoxy) phenyl)ethyl)-2-(3,3-difluoro-1-hydroxycyclobutyl)acetamide; (R)—N-(2-cyclopropoxy-1- (3-(difluoromethoxy) phenyl)ethyl)-2-(3,3-difluoro-1-hydroxycyclobutyl)acetamide; (R)-2- (3,3-difluoro-1-hydroxycyclobutyl)-N-(1-(3-(difluoromethoxy)phenyl)-2- (trifluoromethoxy)ethyl)acetamide; 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.

[0175] 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)propanamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3- (difluoromethoxy)phenyl)ethyl)-3-hydroxy-3-(1-(trifluoro-methyl)cyclopropyl)propanamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxy-3-(1- (trifluoromethyl)cyclopropyl)propanamide; (S)—N—((R)-2-(difluoromethoxy)-1-(3- (trifluoromethoxy)phenyl) ethyl)-3-hydroxy-3-(1-(trifluoromethyl)cyclopropyl) propanamide; (R)-3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)-1-(3- (difluoromethoxy)phenyl)ethyl)-3-hydroxypropanamide; (S)-3-(3,3-difluorocyclobutyl)-N— ((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxypropanamide; (R)- 3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl) ethyl)-3-hydroxypropanamide; (S)-3-(3,3-difluorocyclobutyl)-N—((R)-2-(difluoromethoxy)- 1-(3-(trifluoromethoxy)phenyl)ethyl)-3-hydroxypropanamide; (S)-3-(3,3-difluorocyclobutyl)- N—((S)-1-(3-(difluoromethoxy)phenyl)butyl)-3-hydroxypropanamide; (R)-3-(3,3- difluorocyclobutyl)-N—((S)-1-(3-(difluoromethoxy) phenyl)butyl)-3-hydroxypropanamide;(S)—N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-(1- ethylcyclopropyl)-3-hydroxypropanamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3- (difluoromethoxy)phenyl) ethyl)-3-(1-ethylcyclopropyl)-3-hydroxypropanamide; (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)phenyl) ethyl)acetamide; (R)-2-(3,3-difluoro-1-hydroxycyclobutyl)-N- (2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)acetamide; (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-(trifluoromethoxy) phenyl)propyl)acetamide; (S)—N-(3,3-difluoro-1-(3-(trifluoromethoxy)phenyl)propyl)-2-(3,3-difluoro-1- hydroxycyclobutyl)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-(trifluoromethoxy)phenyl)ethyl)-3-(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-hydroxypropanamide; (R)—N—((R)-2-(difluoromethoxy)-1-(3- (difluoromethoxy)phenyl)ethyl)-3-(3,3-dimethylcyclobutyl)-3-hydroxypropanamide; (S)-3- cyclopentyl-N—((R)-2-(difluoromethoxy)-1-(3-(difluoromethoxy)phenyl)ethyl)-3- hydroxypropanamide; (R)-3-cyclopentyl-N—((R)-2-(difluoromethoxy)-1-(3- (difluoromethoxy)phenyl)ethyl)-3-hydroxypropanamide; (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 a pharmaceutically acceptable salt of any of these compounds.

[0176] In further embodiments, the Kv7 channel activator is a compound according to formula 8 wherein R1is selected from the group consisting of C1-C6alkyl, CF3, CH2CF3, CF2CHF2, C3-C8cycloalkyl, wherein said C3-C8cycloalkyl may be substituted with 1 or 2 F, CHF2or CF3, and R2is H, C1-C6alkyl or CF3; or R1and R2combine to form C3-C5cycloalkyl optionally substituted with 1 or 2 F, CHF2or CF3; R3is C1-C3 alkyl or CH2O—C1-3 alkyl, said C1-C3alkyl or CH2O—C1-3alkyl may optionally be substituted with 1 or 2 F; and R4is selected from the group consisting of OCF3, OCH2CF3or OCHF2.

[0177] In further embodiments, R4is OCF3or OCHF2.

[0178] In further embodiments, R2is H or CH3.

[0179] In further embodiments, R3is CH2O—C1-3alkyl.

[0180] In further embodiments, R1is C3-C4cycloalkyl optionally substituted with 1 or 2 F, CHF2or CF3.

[0181] In further embodiments, R1is t-butyl and R2is H and R4is OCF3, OCH2CF3, OCHF2or CF3.

[0182] In further embodiments, R1and R2combine to form cyclobutyl optionally substituted with 1 or 2 F and R4is OCF3, OCH2CF3, OCHF2or CF3.

[0183] 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, (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- dimthyl-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- difluorocyclobutyl)-3-hydroxy-N-((S)- 1-(3-(trifluoromethoxy)phenyl)ethyl)propanamide, (R)-3-(3,3-difluorocyclobutyl)-3-hydroxy-N-((S)- 1-(3- (trifluoromethoxy)phenyl)ethyl)propanamide, (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-(trifluoro- methoxy)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)-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, 4,4,4-Trifluoro-3-hydroxy-N- [(1S)-1-[3- (trifluoromethoxy)phenyl]ethyl]-3- (trifluoromethyl)butanamide, (R)-4,4,5,5- tetrafluoro-3-hydroxy-3-methyl-N- ((S)-1-(3- (trifluoromethoxy)phenyl)ethyl)pentanamide, (S)-4,4,5,5-tetrafluoro-3-hydroxy-3-methyl-N- ((S)-1-(3- (trifluoromethoxy)phenyl)ethyl)pentanamide, (R)-5,5,5-trifluoro-3-hydroxy-3-methyl-N-((S)- 1- (3-(trifluoromethoxy)phenyl)ethyl)pentanamide, (S)-5,5,5-trifluoro-3-hydroxy-3-methyl- N-((S)-1- (3-(trifluoro methoxy)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. Formula 10

[0184] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 10. Such compounds are described in International Publication No. WO2009015667A1, published February 5, 2009, and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; International Publication No. WO2004058739A1, published July 15, 2004 and corresponding to International Application No. PCT / DK2003 / 000906 filed December 18, 2003; US patent No.7,368,472 issued May 6, 2008 and corresponding to US Application No.10 / 540,075 filed December 18, 2003; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No.12 / 671,505 filed July 31, 2008; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 8, these references incorporated by reference herein control.

[0185] In an embodiment, the Kv7 channel activator is a compound according to formula 10:wherein R1is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8-Cycloalk(en)yl; R2and R2′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, aryl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8- cycloalk(en)yl; R3is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl,C3-8- cycloalk(en)yl, aryl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl-C3-6-alk(en / yn)yl, hydroxy- C1-6-alk(en / yn)yl, aryl-C3-8-cycloalk(en)yl, NR10R10′—C1-4-alk(en / yn)yl, NR10R10′—C3-8-Cycloalk(en)yl and hydroxy-C3-8-cycloalk(en)yl; wherein: R10and R10′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R10and R10′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; X is CO or SO2; Z is O or NR4, wherein: R4is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8-cycloalk(en)yl; or R3and R4together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms, and the ring formed by R3and R4and the nitrogen atom is optionally substituted with one or more substituents independently selected from C1-6-alk(en / yn)yl, aryl and aryl-C1-6-alk(en / yn)yl; q is 0 or 1; and Y represents a heteroaryl of one of the following formulas:wherein: 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 R5is independently selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, aryl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, acyl, halogen, halo-C1-6- alk(en / yn)yl, alk(en / yn)yloxy, —CO—NR6R6′, cyano, nitro, —NR7R4′, —S—R8, —SO2R8, and SO2OR8; wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and aryl; R7and R7′are independently selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and acyl; and R8is selected from the group consisting of C1-6-alk(en / yn)yl, C1-6-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and NR9R9′; wherein: R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or a pharmaceutically acceptable salt thereof.

[0186] 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; {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- thiophen-2-ylmethyl)-ethyl-amino]-phenyl}-carbamic acid ethyl ester; {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.

[0187] In further embodiments, the Kv7 channel activator is a compound according to the formula:or a pharmaceutically acceptable salt thereof.

[0188] 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.

[0189] In further embodiments, the Kv7 channel activator is a compound according to formula 10 wherein: R1is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8-cycloalk(en)yl; R2and R2′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, aryl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8- cycloalk(en)yl; R3is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, aryl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, hydroxy- C1-6-alk(en / yn)yl, aryl-C3-8-cycloalk(en)yl, NR10R10′—C1-6-alk(en / yn)yl, NR10R10′—C3-8- cycloalk(en)yl and hydroxy-C3-8-cycloalk(en)yl, wherein: R10and R10′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, or R10and R10′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; X is CO or SO2; Z is Oor NR4, wherein: R4is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8-cycloalk(en)yl; or R3and R4together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms, the ring formed by R3and R4and the nitrogen atom is optionally substituted with one or more substituents independently selected from C1-6-alk(en / yn)yl, aryl and aryl-C1-6-alk(en / yn)yl; q is 0 or 1; and Y represents a heteroaryl of formula:, wherein: 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 R5is independently selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, aryl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, acyl, halogen, halo-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, —CO—NR6R6′, cyano, nitro, —NR7R7′, —S—R8, —SO2R8, and SO2OR8, wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and aryl; R7and R7′are independently selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and acyl; and R8is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and —NR9R9′, wherein: R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or a pharmaceutically acceptable salt thereof.

[0190] In further embodiments, R1is selected from the group consisting of hydrogen and C1-6-alk(en / yn)yl.

[0191] In further embodiments, at least one of the substituents R2and R2′is a hydrogen atom.

[0192] In further embodiments both R2and R2′are hydrogen atoms.

[0193] In further embodiments, X is CO.

[0194] In further embodiments, q is 0.

[0195] In further embodiments, q is 1 and Z is an oxygen atom.

[0196] In further embodiments, R3is selected from the group consisting of C1-6-alk(en / yn)yl and aryl-C1-6-alk(en / yn)yl.

[0197] In further embodiments, R3is C1-6-alk(en / yn)yl.

[0198] In further embodiments, R3is aryl-C1-6-alk(en / yn)yl.

[0199] In further embodiments, W is a sulfur atom.

[0200] In further embodiments, Y is of formula:, wherein: 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 R5is independently selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, aryl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, acyl, halogen, halo-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, —CO—NR6R6′, cyano, nitro, —NR7R7′, —S—R8, —SO2R8, and SO2OR8, wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and aryl; R7and R7′are independently selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and acyl; and R8is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and —NR9R9′, wherein: R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl.

[0201] In further embodiments, Y is of formula:, wherein: 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 R5is independently selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, aryl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl-C1-6-alk(en / yn)yl, acyl, halogen, halo-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, —CO—NR6R6′, cyano, nitro, —NR7R7′, —S—R8, —SO2R8, and SO2OR8, wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and aryl; R7and R7′are independently selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and acyl; and R8is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, aryl and —NR9R9′, wherein: R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl. Formula 11 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 11. Such compounds are described in International Publication No. WO2009015667A1, published February 5, 2009, and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; International Publication No. WO2004058739A1, published July 15, 2004 and corresponding to International Application No. PCT / DK2003 / 000906 filed December 18, 2003; US patent No. 7,368,472 issued May 6, 2008 and corresponding to US Application No.10 / 540,075 filed December 18, 2003; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No.12 / 671,505 filed July 31, 2008; International Publication No. WO2004082677A1, published September 30, 2004 and corresponding to International Application No. PCT / DK2004 / 000186 filed March 18, 2004; InternationalPublication No. WO2004080950A1, published or issued September 23, 2004 and corresponding to International Application No. PCT / DK2004 / 000162 filed March 12, 2004; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 11, these references incorporated by reference herein control.

[0202] In an embodiment, the Kv7 channel activator is a compound according to formula 11: Formula 11wherein: s is 0 or 1; U is O, S, SO2, SO2NR11, CO—O or CONR11; wherein: R11is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, and C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl; or R2and R11together with the nitrogen atom to which R11is attached form a 5-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; q is 0 or 1; X is CO or SO2; with the proviso when X is SO2, then q is 0; Z is O or S; R1is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6- alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; R2is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar— C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halogen, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, NR10R10′—C1-6-alk(en / yn)yl, NR10R10′—C3-8-cycloalk(en)yl and NR10R10′—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein: R10and R10′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yl; or R10and R10′together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring that optionallycontains 1, 2 or 3 further heteroatoms; and provided that: when R2is halogen or cyano, then s is 0; and when s is l and R2is a hydrogen atom or acyl, then U is O or S; R3is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, heterocycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yl- heterocycloalk(en)yl, heterocycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar— C3-8-cycloalk(en)yl, Ar-heterocycloalk(en)yl, Ar—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar—C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, Ar—C1-6-alk(en / yn)yl-heterocycloalk(en)yl, C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C1-6- alk(en / yn)yloxy-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yloxy-heterocycloalk(en)yl, Ar-oxy-C1-6- alk(en / yn)yl, Ar—C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycl oal k(en)yl-C1-6- alk(en / yn)yl oxy-carbonyl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, hydroxy-heterocycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl- heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo- heterocycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl-C3-8- cycloalk(en)yl, halo-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl-Ar, halo- C3-8-cycloalk(en)yl-Ar, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl-Ar, halo-C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl-Ar, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano- heterocycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl, cyano-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, acyl-C1-6-alk(en / yn)yl, acyl-C3-8-cycloalk(en)yl, acyl-heterocycloalk(en)yl, acyl-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, acyl-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, acyl-C1-6-alk(en / yn)yl- heterocycloalk(en)yl, NR12R12′, optionally substituted NR12R12′—C1-6-alk(en / yn)yl, optionally substituted NR12R12′—C3-8-cycloalk(en)yl, and optionally substituted NR12R12′—C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein: R12and R12′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, Ar-heterocycloalk(en)yl, Ar-oxy-C1-6-alk(en / yn)yl, Ar-oxy-C3-8- cycloalk(en)yl, Ar-oxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar-oxy-heterocycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, halo-C1-6-alk(en / yr)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl; or R12and R12′together with the nitrogen atom to whichthey are attached form a 5-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; provided that: when R3is NR12R12′, then q is 0; and Y represents a group of the following formulas:wherein: the line represents a bond attaching the group represented by Y to the 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 R5is independently selected from the group consisting of a C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6- alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar-oxy, Ar-oxy-C1-6-alk(en / yn)yl, Ar-oxy-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yl-heterocycloalk(en)yl, Ar-oxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, C1-6-alk(en / yn)yloxy, C3-8- cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, C1-6-alk(en / yn)yloxy-carbonyl, halogen, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, —CO—NR6R6′, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, NR7R7′, S—R8and SO2R8; or two adjacent R5together with the aromatic group form a 5-8 membered ring that optionally contains one or two heteroatoms; wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and Ar; R7and R7′are independently selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, heterocycloalk(en)yl-C1-6-alk(en / yn)yl, heterocycloalk(en)yl-C3-8-cycloalk(en)yl, heterocycloalk(en)yl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, heterocycloalk(en)yl-Ar and acyl; or R7and R7′together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; and R8is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycl oalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar and —NR9R9′; wherein R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or a pharmaceutically acceptable salt thereof.

[0203] 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- benzenesulfonyl)-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- benzenesulfonyl)-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 propylester; {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 ester; {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 ethylester; [2- Cyclopentyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]-carbamic acid ethyl ester; [4-(3- Fluoro-2-methylbenzylamino)-2-phenethyloxyphenyl]-carbamic acid ethyl ester; [2- Benzyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl]carbamic acid ethyl ester; [2- Benzyloxy-4-(4-methylsulfanylbenzylamino)-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]dioxol-5-ylmethyl)-amino]-2-isopropoxyphenyl}-carbamic acid ethyl ester; {4- [(5-Bromo-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-methyl phenyl}-carbamic acid propyl ester; {4-[(4- Isopropylbenzyl)-(methyl)amino]-2-methyl phenyl}-carbamic acid propyl ester; {2-Methyl- 4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester; {2-Methyl- 4-[methyl-(4-methylsulfanyl-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-methylsulfanyl-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-trifluoromethyl-benzyl)-amino]-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-methylsulfanyl- 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-methylsulfanyl-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-methylsulfanyl-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-ylmethylyamino]-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-Methylsulfanyl-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]-carbamic acid propyl ester; [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-Methylsulfanyl-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]-carbamic acid propyl ester; {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-methylsulfanyl- 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]- 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-dimethylbutyramide; N-{2-Chloro-4-[(5-chloro-thiophen-2- ylmethyl)-(methyl)amino]-phenyl}-3-phenylpropionamide; N-{2-Chloro-4-[(5-chloro- thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-butyramide; Pentanoic acid {2-chloro-4-[(5- chloro-thiophen-2-ylmethyl)-(methyl)amino]-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-(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-dimethylpropionamide; 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-phenyl acetamide; N-{2-Chloro-4-[(5-chloro- thiophen-2-ylmethyl)-amino]-phenyl}-3,3-dimethylbutyramide; N-{2-Chloro-4-[(5-chloro- thiophen-2-ylmethyl)-amino]-phenyl}-butyramide; Pentanoic 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)-acetamide; 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]dioxine-6-carboxyl 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-phenyl acetamide; N-{4-[(5-Chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-3,3- dimethylbutyramide; 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-methyl phenyl}-amide; Cyclohexanecarboxylic acid {4-[(5-chloro-thiophen-2-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-methyl phenyl}-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-methyl phenyl}-2-(4-methoxyphenyl)-acetamide; N-{4-[(5-Chloro-thiophen-2-ylmethyl)- (methyl)amino]-2-methyl phenyl}-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 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-trifluoromethyl-benzylamino)-2- methylphenyl]-carbamic acid ethyl ester; 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; Pentanoic 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; {2-Benzyloxy-4-[(4-fluorobenzyl)- (methyl)amino]-phenyl}-thiocarbamic acid S-ethyl ester; {2-Cyclopentyloxy-4-[(4- fluorobenzyl)-(methyl)amino]-phenyl}-thiocarbamic acid S-ethyl ester; 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; {4-[(5-Chloro-thiophen-2- ylmethyl)-amino]-2-pyridin-3-yl-phenyl}-carbamic acid ethyl ester; 1-Amino- cyclopropanecarboxylic acid [2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-amide; {4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-pyridin-4-yl-phenyl}-carbamic acid ethyl ester; N-[2-Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-piperidin-1-yl-acetamide; N-(4-{[5-(4-Chlorophenoxy)-1,3-dimethyl-1H-pyrazol-4-ylmethyl]-amino}-2- methylphenyl)-2,2-dimethylpropionamide; 2,2-Dimethyl-N-{2-methyl-4-[(6-phenoxypyridin- 3-ylmethyl)-amino]-phenyl}-propionamide; N-[2-Methyl-4-(4-trifluoromethyl-benzylamino)- phenyl]-2-pyrrolidin-1-yl-acetamide; [4-[(5-Chloro-thiophen-2-ylmethyl)-amino]-2-(6- methoxypyridin-3-yl)-phenyl]-carbamic acid ethyl ester; 4-[(3-Methyl-4- propoxycarbonylamino-phenyl amino)-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.

[0204] In further embodiments, the Kv7 channel activator is a compound according to formula 11, wherein: s is 0 or 1; U is O, S, SO2, SONR11, or CONR11; wherein: R11is hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, or C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R2and R11taken together with the nitrogen atom form a 5-8 membered saturated or unsaturated ring, which optionally contains 1, 2 or 3 further heteroatoms; q is 0 or 1; X is CO or SO2; with the proviso that q is 0 when X is SO2; Z is O or S; R1is hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6- alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo -C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en) yl or cyano-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl; R2is hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk (en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halogen, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk (en)yl, halo -C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8cycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, NR10R10′—C1-6-alk(en / yn)yl, NR10R10′—C3-8-cycloalk(en)yl or NR10R10′—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein: R10and R10′are each independently hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl or cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R10and R10′taken together with the nitrogen atom form a 5-8 membered saturated or unsaturated ring, which optionally contains 1, 2 or 3 further heteroatoms; with the proviso that: when R2is halogen or cyano, then s is 0; and when s is 1 and R2is a hydrogen atom or acyl, then U is O or S; R3is C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, heterocycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yl-heterocycloalk(en)yl, heterocycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-C3-8-cycloalk(en)yl, C1-6- alk(en / yn)yloxy-heterocycloalk(en)yl, C1-6-alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy - carbonyl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-heterocycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6- alk(en / yn)yl -C3-8-cycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, halo -C3-8- cycloalk(en)yl, halo-heterocycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo - C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, halo-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-heterocycloalk(en)yl, cyano-C3-8- cycloalk(en)yl -C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, cyano-C1-6- alk(en / yn)yl -heterocycloalk(en)yl, acyl-C1-6-alk(en / yn)yl, acyl-C3-8-cycloalk(en)yl, acyl- heterocycloalk(en)yl, acyl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl-C1-6-alk(en / yn)yl-C3-8- cycloalk(en)yl, acyl-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, NR12R12′, optionally substituted NR12R12′-C1-6-alk(en / yn)yl, optionally substituted NR12R12′-C3-8-alk(en / yn)yl, or optionally substituted NR12R12′-C3-8-alk(en / yn)yl-C1-6-alk(en / yn)yl; wherein: R12and R12′are each independently hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, Ar-heterocycloalk(en)yl, Ar-oxy-C1-6-alk(en / yn)yl, Ar-oxy-C3-8- cycloalk(en)yl, Ar-oxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar-oxy -heterocycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, or cyano -C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl; or R12and R12′taken together with the nitrogen atom form a 5-8 membered saturated or unsaturated ring, which optionally contains 1, 2 or 3 further heteroatoms; with the proviso that when R3is NR12R12′then q is 0; and Y is a group of formula:, wherein: “|” represents a bond attaching the group represented by Y to the carbon atom; V is C or CH; and k is 0, 1, 2 or 3; and each R5is independently C1-6-alk(en / yn)yl, C3-8-cycloalk (en)yl, C3-8-cycloalk(en) yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8- cycloalk(en)yl, Ar—C3-8-cycloalk (en)yl-C1-6-alk(en / yn)yl , Ar-oxy, Ar-oxy-C1-6alk(en / yn)yl, Ar-oxy-C3-8-cycloalk(en)yl, C1-6-alk (en / yn)yl -heterocycloalk(en)yl, Ar-oxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, C1-6-alk (en / yn)yloxy, C3-8-cycloalk(en)yloxy, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yloxy, C1-6-alk(en / yn)yloxy-carbonyl, halogen, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, —CO— NR6R6′, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk (en)yl, cyano-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, NR7R7′, S—R8or SO2R8; or two adjacent R5groups taken together with the aromatic group form a 5-8 membered ring, which optionally contains one or two heteroatoms; wherein: R6and R6′are each independently hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl or Ar; R7and R7′are each independently hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar, heterocycloalk(en)yl-C1-6-alk (en / yn)yl, heterocycloalk(en)yl-C3-8- cycloalk(en)yl, heterocycloalk(en)yl-C3-8-cycloalk(en)yl-C1-6-alk (en / yn)yl, heterocycloalk(en)yl-Ar or acyl; or R7and R7′taken together with the nitrogen atom form a 5- 8 membered saturated or unsaturated ring which optionally contains 1, 2 or 3 further heteroatoms; and R8is hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, Ar or —NR9R9′; wherein: R9and R9′are each independently hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl or C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or salts thereof.

[0205] In further embodiments, R1is C1-6-alk(en / yn)yl or a hydrogen atom.

[0206] In further embodiments, s is 0.

[0207] In further embodiments, s is 1.

[0208] In further embodiments, U is an oxygen atom.

[0209] In further embodiments, R2is hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, Ar, Ar—C1-6-alk(en / yn)yl, halogen, halo-C1-6-alk(en / yn)yl or cyano; with the provisos that when R2is halogen or cyano, then s is 0; and when s is 1 and R2is a hydrogen atom, then U is O or S.

[0210] In further embodiments, Z is an oxygen atom.

[0211] In further embodiments, Z is a sulfur atom.

[0212] In further embodiments, q is 0.

[0213] In further embodiments, q is 1.

[0214] In further embodiments, X is CO.

[0215] In further embodiments, R3is C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, heterocycloalk (en)yl-C1 -6-alk(en / yn)yl, heterocycloalk(en)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar-oxy-C1-6-alk (en / yn)yl, Ar—C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, NR12R12′, optionally substituted NR12R12′—C1-6-alk(en / yn)yl, or optionally substituted NR12R12′—C3-8-cycloalk(en)yl.

[0216] In further embodiments, R12and R12′are each independently hydrogen, C1-6- alk(en / yn)yl or Ar.

[0217] In further embodiments, V is CH.

[0218] In further embodiments, each R5is independently C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl- heterocycloalk(en)yl, Ar, C1-6-alk(en / yn)yloxy, Ar-oxy, C1-6-alk(en / yn)yloxy-carbonyl, halogen, halo-C1-6-alk(en / yn)yl, NR7R7′, S—R8or SO2R8; or two adjacent R5groups taken together with the aromatic group form a 5-8 membered ring, which optionally contains one or two heteroatoms.

[0219] In further embodiments, both R7and R7′are C1-6-alk(en / yn)yl.

[0220] In further embodiments, R8is C1-6-alk(en / yn)yl or Ar.

[0221] 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 }-proprionamide; or a salt thereof.

[0222] In further embodiments, the Kv7 channel activator is a compound according to formula 11 wherein: U is O, S or NR2′; s is 0 or 1; X is CO or SO2; Z is O, S or NR4; wherein R4is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl and hydroxy-C3-8- cycloalk(en)yl; q is 0 or 1; R1and R1′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, halo-C1-6-alk(en / yn)yl and halo-C3-8- cycloalk(en)yl; R2is selected from the group consisting of hydrogen, halogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6- alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl and cyano; provided that: when R2is halogen or cyano, then s is 0; and when s is 1 and U is NR2′, then R2′is selectedfrom the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, halo-C1-6-alk(en / yn)yl and halo-C3-8- cycloalk(en)yl; or R2and R2′together form a 5-8 membered saturated or unsaturated ring that optionally contains one further heteroatom; R3is selected from the group consisting of C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6- alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, halo-C1-6-alk(en / yn)yl and halo-C3-8-cycloalk(en)yl; and Y represents a group of the following formulas:wherein: the line represents a bond attaching 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 R5is independently selected from the group consisting of a C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, Ar, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar—C1-6-alk(en / yn)yl, acyl, C1-6-alk(an / en / yn)yloxy, halogen, halo-C1-6-alk(en / yn)yl, —CO—NR6R6′, cyano, nitro, —NR7R7′, —S—R8and SO2OR8; or two adjacent R5substituents together with the aromatic group form a 5-8 membered saturated or unsaturated ring that optionally contains one or two heteroatoms; wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and Ar; R7and R7′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar and acyl; and R8is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar and —NR9R9′; wherein R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl; with the provisos that; when R5is SO2OR8then R8is not —NR9R9′; and when R5is SO2R8, then R8is not a hydrogen atom; or a pharmaceutically acceptable salt thereof; with the proviso 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-pyridinyl)- benzamide; N- [4- [ [(3 ,4, 5- trimethoxyphenyl)amino]methyl]phenyl] -acetamide; N-[4-[[(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2- naphthalenyl)amino]methyl]phenyl]-acetamide; N-[4-[[[3-(lH-imidazol-l- ylmethyl)phenyl]amino]methyl]phenyl]- acetamide; N-[4-[[[2-(lH-imidazol-l- 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.

[0223] In further embodiments, R1and R1' are independently selected from the group consisting of hydrogen and C1-6-alk(en / yn)yl.

[0224] In further embodiments, at least one of R1and R1' is a hydrogen atom. In further embodiments, s is 1.

[0225] In further embodiments, s is 0.

[0226] In further embodiments, R2is selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, Ar and halogen, provided that when R is halogen, then s is 0.

[0227] In further embodiments, U is NR2' and at least one of R and R2' is a hydrogen atom.

[0228] In further embodiments, both R2and R2are hydrogen atoms.

[0229] In further embodiments, X is CO.

[0230] In further embodiments, q is 0.

[0231] In further embodiments, q is 1.

[0232] In further embodiments, Z is an oxygen atom.

[0233] In further embodiments, R3is C1-6- alk(en / yn)yl.

[0234] In further embodiments, each R5is independently selected from the group consisting of a C1-6-alk(en yn)yl, C3-8- cycloalk(en)yl, Ar, cyano, halogen, halo-Cι-6-alk(en / yn)yl and C1-6- alk(an / en / yn)yloxy or two adjacent substituents together form a 5-8 membered saturated or unsaturated ring which optionally contains one or two heteroatoms.

[0235] In further embodiments, the Kv7 channel activator is selected from the group consisting of: {2-Amino-4-[(4-tert-butyl phenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; (2-Amino-4-phenylaminomethyl-phenyl)-carbamic acid ethyl ester; [2-Amino-4- (aphthalene-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}- carbamic acid ethyl ester; {2-Amino-4-[(4-fluorophenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; {2-Amino-4-[(2-fluorophenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; [2-Amino-4-(biphenyl-4-ylaminomethyl)-phenyl]-carbamic acid ethyl ester; {2-Amino- 4-[(2,4-difluorophenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; {2-Amino-4-[(4- methoxyphenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; {2-Amino-4-[(4- cyclohexylphenylamino)-methyl]-phenyl}-carbamic acid ethyl ester; [2-Amino-4-(indan-5- ylaminomethyl-phenyl]-carbamic acid ethyl ester; {2-Amino-4-[(4-isopropylphenylamino)- methyl]-phenyl}-carbamic acid ethyl ester; {2-Amino-4-[(4-butylphenylamino)-methyl]- phenyl}-carbamic acid ethyl ester; {2-Amino-4-[(4-chloro-3- fluorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(2,4- dichlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(2,3- dichlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(3,5- dichlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(3,4- dichlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(3-trifluoromethylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(3- fluoro-4-trifluoromethylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4- [(3,4-dichlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(4- cyanophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(4-fluoro-3- trifluoromethylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(3- chloro-4-methylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[(3- chlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; [2-Amino-4-(m- tolylaminomethyl)phenyl]carbamic acid ethyl ester; {2-Amino-4-[1-(4- chlorophenylamino)ethyl]phenyl}carbamic acid ethyl ester; {2-Amino-4-[1-(4- trifluoromethylphenylamino)ethyl]phenyl}carbamic acid ethyl ester; N-{2-Amino-4-[(3- fluorophenylamino)methyl]phenyl}-2,2-dimethylpropionamide; {4-[(4- Chlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {4-[(4- Trifluoromethylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {4-[(4- Chlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {4-[(4- Fluorophenylamino)methyl]-2-methylphenyl}carbamic acid ethyl ester; {4-[(4- Chlorophenylamino)methyl]-2-methylphenyl}carbamic acid ethyl ester; {2-Methyl-4-[(4- trifluoromethylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {4-[(3,4- Difluorophenylamino)methyl]-2-methylphenyl}carbamic acid ethyl ester; {4-[(3- Fluorophenylamino)methyl]-2-methylphenyl}carbamic acid ethyl ester; {2-Chloro-4-[(4- chlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Chloro-4-[(4- trifluoromethyl-phenylamino)-methyl]phenyl}-carbamic acid ethyl ester; {2-Chloro-4-[(4- fluorophenylamino)methyl]phenyl}-carbamic acid ethyl ester; {2-Chloro-4-[(3- fluorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Chloro-4-[(3,4- dichlorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {2-Chloro-4-[(4-chloro-3- fluorophenylamino)methyl]phenyl}carbamic acid ethyl ester; {4-[(4- Chlorophenylamino)methyl]-2-fluorophenyl}carbamic acid ethyl ester; {4-[(4-Chloro-3- fluorophenylamino)methyl]-2-fluorophenyl}carbamic acid ethyl ester; {2-Fluoro-4-[(4- trifluoromethylphenylamino)methyl]phenyl}carbamic acid ethyl ester; {4′-Dimethylamino-5- [(3-fluorophenylamino)methyl]biphenyl-2-yl}carbamic acid ethyl ester; {4′-Dimethylamino- 5-[(4-trifluoromethylphenylamino)methyl]biphenyl-2-yl}carbamic acid ethyl ester; {4′- Chloro-5-[(3-fluorophenylamino)methyl]biphenyl-2-yl}carbamic acid ethyl ester; {4′- Chloro-5-[(4-trifluoromethylphenylamino)methyl]biphenyl-2-yl}carbamic acid ethyl ester; N-{4-[(4-chlorophenylamino)methyl]phenyl}butyramide; N-{4-[(3,4- dichlorophenylamino)methyl]phenyl}butyramide; N-{4-[(4-chloro-3-fluorophenylamino)methyl]phenyl}butyramide; N-{4-[(4-fluoro-phenylamino)methyl]-2- methyl phenyl}butyramide; N-{4-[(3-fluorophenylamino)methyl]-2- methylphenyl}butyramide; N-{4-[(4-chlorophenylamino)methyl]-2- methylphenyl}butyramide; N-{4-[(3,4-dichlorophenylamino)methyl]-2- methylphenyl}butyramide; N-{4-[(4-chloro-3-fluorophenylamino)methyl]-2-methyl phenyl}butyramide; N-{2-chloro-4-[(4- trifluoromethylphenylamino)methyl]phenyl}butyramide; N-{2-chloro-4-[(4- fluorophenylamino)methyl]phenyl}butyramide; N-{2-chloro-4-[(3- fluorophenylamino)methyl]phenyl}butyramide; N-{2-chloro-4-[(4- chlorophenylamino)methyl]phenyl}butyramide; N-{2-chloro-4-[(3,4- dichlorophenylamino)methyl]phenyl}butyramide; N-{2-chloro-4-[(4-chloro-3- fluorophenylamino)methyl]phenyl}butyramide; N-{2-fluoro-4-[(3- fluorophenylamino)methyl]phenyl}butyramide; N-{4-[(4-chlorophenylamino)methyl]-2- fluorophenyl}butyramide; N-{2-fluoro-4-[(4- trifluoromethylphenylamino)methyl]phenyl}butyramide; N-{-4-[(3,4- dichlorophenylamino)methyl]-2-fluorophenyl}butyramide; N-{4-[(4-chloro-3- fluorophenylamino)methyl]-2-fluorophenyl}butyramide; and pharmaceutically acceptable salts thereof.

[0236] In further embodiments, 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 R4is selected from the group consisting of hydrogen, Cι-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en yn)yl and hydroxy-C3-8- cycloalk(en)yl; q is O or 1; R1and R1' are independently selected from the group consisting of hydrogen, C\.6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-Cι-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, halo-C1-6-alk(en / yn)yl and halo-C3-8-cycloalk(en)yl; R is selected from the group consisting of hydrogen, halogen, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-Cι-6-alk(en / yn)yl, Ar, Ar-C1-6- alk(en / yn)yl, Ar-C3-8-cycloalk(en)yl, acyl, hydroxy-Cι-6-alk(en / yn)yl, hydroxy- C3-8- cycloalk(en)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl and cyano; provided that when R2is halogen or cyano then s is 0; when s is 1 and U is NR2' then R2' is selected from the group consisting of hydrogen, C1-6-alk(en yn)yl, C-8-cycloalk(en)yl, C3-8-cycloallc(en)yl- Cι-6- alk(en / yn)yl, Ar, Ar-C1-6-alk(en / yn)yl, Ar-C3-8-cycloalk(en)yl, acyl, hydroxy- ..6- alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, halo-C1-6-alk(en / yn)yl and halo-C3-8- cycloalk(en)yl; or R2and R2' together form a 5-8 membered saturated or unsaturated ringwhich optionally contains one further heteroatom; R3is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-Cι-6-alk(en / yn)yl, Ar, Ar-C1-6- alk(en / yn)yl, Ar-C3-8- cycloalk(en)yl, hydroxy-Cι-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, halo-Cj.6-alk(en / yn)yl and halo-C3-8-cycloalk(en)yl; and Y is selected from groups according to a formula selected from the group consisting of:wherein: the line represents a bond attaching the group represented by Y to the nitrogen atom; W is O or S; a is 0, 1, 2 or 3; b is O, 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 O, 1, 2, 3, 4 or 5; g is 0, 1, 2, 3 or 4; h is 0, 1, 2 or 3; and each R5is independently selected from the group consisting of a C1-6- alk(en yn)yl, C3-8-cycloalk(en)yl, Ar, C3-8- cycloalk(en)yl-C1-6-alk(en yn)yl, Ar- Cι-6-alk(en / yn)yl, acyl, C1-6-alk(an / en / yn)yloxy, halogen, halo-Cι-6-alk(en / yn)yl, -CO-NR6R6', cyano, nitro, -NR7R7', -S-R8, -SO2R8and SO2OR8, or two substituents together form a 5-8 membered saturated or unsaturated ring which optionally contains one or two heteroatoms; R6and R6' are independently selected from the group consisting of hydrogen, C\.6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl and Ar; R7and R7' are independently selected from the group consisting of hydrogen, C\.6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar and acyl; and R8is selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-Cι-6-alk(en / yn)yl, Ar and -NR9R9; wherein R9and R9' are independently selected from the group consisting of hydrogen, C6- alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; with the provisosthat when R5is SO2OR8then R8is not -NR9R9'and when R5is SO2R8, then R8is not a hydrogen atom; or salts thereof; with the proviso that the compound of formula I is not: 2- [[[4-(acetylamino)phenyl]methyl]amino]-5-chloro-N-(5-chloro-2-pyridinyl)- benzamide; N- [4-[[(3,4,5-trimethoxyphenyl)amino]methyl]phenyl]-acetamide; N-[4-[[(5,6,7,8-tetrahydiO- 5,5,8,8-tetramethyl-2- naphthalenyl)amino]methyljρhenyl]-acetamide; N- [4- [ [[3 -( 1 H- imidazol- 1 -ylmethyl)phenyl]amino]methyl]phenyl] - acetamide; N-[4-[[[2-(lH-imidazol-l- ylmethyl)phenyl]amino]methyl]phenyl]-acetamide; N-[4-[[[4-( IH-imidazol- 1 - ylmethyl)phenyl]amino]methyl]phenyl]- acetamide; N-[4-[[(4-amino-3,5- dichlorophenyl)ammo]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.

[0237] In further embodiments, the Kv7 channel activator is a compound according to formula 11 wherein: wherein U is O, S or NR2s 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, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-s-cycloaUc(en)yl-Cι-6-alk(en / yn)yl, hydroxy-Cι-6-alk(en / yn)yl and hydroxy-C3-8-cycloalk(en)yl; q is O or 1; 11 ' R and R are independently selected from the group consisting of hydrogen, Cι_6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl- C1.6-alk(en / yn)yl, acyl, hydroxy-Cι-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, halo-C1_.6- alk(en / yn)yl and halo-C3.8-cycloalk(en)yl; R is selected from the group consisting of hydrogen, halogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-Cι-6-alk(en yn)yl, Ar, Ar-Cι-6- alk(en yn)yl, Ar-C3-8-cycloalk(en)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy- C3-8-cycloalk(en)yl, halo-Cι-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl and cyano; provided that when R2is halogen or cyano then s is 0; when s is 1 and U is NR2then R2'is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C-8-cycloalk(en)yl, C .8- cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar, Ar-C1-6-alk(en / yn)yl, Ar-C3.8-cycloalk(en)yl, acyl, hydroxy-C^6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, halo-C1-6-alk(en / yn)yl and halo-C3-8- cycloalk(en)yl; or R and R together form a 5-8 membered saturated or unsaturated ring which optionally contains one further heteroatom; R3is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en yn)yl, Ar, Ar-C1-6- alk(en / yn)yl, Ar-C3-8- cycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, halo-Ci-6-alk(en yn)yl and halo-C3-s-cycloalk(en)yl; and Y is selected from groups according to a formula selected from the group consisting of:

[0238] wherein, the line represents a bond attaching 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 O, 1, 2, 3, 4 or 5; is 0, 1, 2, 3 or 4; h is 0, 1, 2 or 3; and each R5is independently selected from the group consisting of a Cι-6- alk(en / yn)yl, C3.8-cycloalk(en)yl, Ar, Cs-s-cycloall^ei^yl-Ci-e-all^en / ^yl, Ar- Cι-6-alk(en / yn)yl, acyl, C1-6-alk(an / en / yn)yloxy, halogen, halo-C1-6-alk(en / yn)yl, -CO-NR6R6', cyano, nitro, -NR7R7', -S-R8, -SO2R8and SO2OR8, or two substituents together form a 5-8 membered saturated or unsaturated ring which optionally contains one or two heteroatoms; R6and R6are independently selected from the group consisting of hydrogen, C\.6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl and Ar; R7and R7' are independently selected from the group consisting of hydrogen, Cj.6-alk(en / yn)yl, C3-8-cycloalk(en)yl, Cs-s-cycloall^en l- -e-all^en / yn l, Ar and acyl; and R8is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar and -NR9R9; wherein R9and R9' are independently selected from the group consisting of hydrogen, Q.6-alk(en / yn)yl, C3-8- cycloalk(en)yl and C3-8-cycloalk(en)yl-Cι-6-alk(en yn)yl; with the provisos that when R5is SO2OR8then R8is not -NR9R9' and when R5is SO2R8, then Rsis not a hydrogen atom; or salts thereof for increasing ion flow in a potassium channel of a mammal such as a human. Formula 12

[0239] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 12. Such compounds are described inInternational Publication No. WO2009015667A1, published February 5, 2009, and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; International Publication No. WO2004096767A1, published November 11, 2004 and corresponding to International Application No. PCT / DK2004 / 000283 filed April 23, 2004; US Publication No. US20060264496A1 published November 23, 2006 and corresponding to US Application No.10 / 551,738 filed April 23, 2003; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No. 12 / 671,505 filed July 31, 2008; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 12, these references incorporated by reference herein control.

[0240] In an embodiment, the Kv7 channel activator is a compound according to formula 12: Formula 12wherein, the dotted line represents an optional bond; R1and R1′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R1and R1′together with the carbon atom to which they are attached form a 3-8 membered saturated or unsaturated ring that optionally contains 1 or 2 heteroatoms; s is 0 or 1; U is O, NR11, S, SO2, SO2NR11, CO—O or CO—NR11; wherein: R11is selected from the group consisting of hydrogen, C1-6- alk(en / yn)yl, C3-8-cycl oal k(en)yl, and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R2and R2′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; R2is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halogen, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, —NO2, NR10R10′—C1-6-alk(en / yn)yl, NR10R10′—C3-8-cycloalk(en)yl and NR10R10′—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein: R10and R10′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-Cl—6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R10and R10′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; with the proviso that; when R2is NO2, halogen or cyano, then s is 0; and when R2, R2is a hydrogen atom or acyl and s is 1, then U is NR11, O or S; wherein the group —(U)s—R2is linked to position 4 or 6 of the indole or indoline; q is 0 or 1; Z is O or S; X is CO or SO2; with the proviso that when q is 0, then X is SO2; R3is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, heterocycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yl-heterocycloalk(en)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar— C3-8-cycloalk(en)yl, Ar-heterocycloalk(en)yl, Ar—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar—C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, Ar—C1-6-alk(en / yn)yl-heterocycloalk(en)yl, C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C1-6- alk(en / yn)yloxy-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yloxy-heterocycloalk(en)yl, Ar-oxy-C1-6- alk(en / yn)yl, Ar—C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, hydroxy-heterocycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl- heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo- heterocycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl-C3-8- cycloalk(en)yl, halo-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl-Ar, halo- C3-8-cycloalk(en)yl-Ar, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl-Ar, halo-C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl-Ar, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano- heterocycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl, cyano-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, acyl-C1-6-alk(en / yn)yl, acyl-C3-8-cycloalk(en)yl, acyl-heterocycloalk(en)yl, acyl-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, acyl-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, acyl-C1-6-alk(en / yn)yl- heterocycloalk(en)yl, —NR12R12′, optionally substituted NR12R12′—C1-6-alk(en / yn)yl,optionally substituted NR12R12′—C3-8-cycloalk(en)yl, and optionally substituted NR12R12′— C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein: R12and R12′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R12and R12′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring that optionally contains 1, 2 or 3 further heteroatoms; with the proviso that when R3is NR12R12′, then q is 0; and Y represents a group of formula from the group:wherein: the line represents a bond attaching the group represented by Y to the 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; with the provisos that: when T is a nitrogen atom, then j is 0, 1, 2 or 3; and when Tis NH or an oxygen atom, then j is 0, 1 or 2; k is 0, 1, 2, 3 or 4; and each R5is independently selected from the group consisting of a C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar-thio, Ar-oxy, acyl, C1-6- alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, halogen, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, —CO—NR6R6′, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, —NR7R7′, —S—R8and —SO2R8; or two adjacent R5substituents together with the aromatic group to which they are attached form a 4-8 membered ring that optionally contains one or two heteroatoms; wherein: R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl and Ar; R7and R7′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar and acyl; and R8is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar and —NR9R9′; wherein R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; provided that when R8is —NR9R9′, then R5is not —S—R8, or a pharmaceutically acceptable salt thereof. with the proviso 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 salts thereof.

[0241] In further embodiments, least one of R1or R1′is a hydrogen atom.

[0242] In further embodiments, R1and R1′are hydrogen atoms.

[0243] In further embodiments, s is 0.

[0244] In further embodiments, s is 1.

[0245] In further embodiments, R2is a hydrogen atom.

[0246] In further embodiments, R2is NO2or a halogen atom.

[0247] In further embodiments, U is NR11.

[0248] In further embodiments, R11is a hydrogen atom.

[0249] In further embodiments, X is CO.

[0250] In further embodiments, X is SO2.

[0251] In further embodiments, q is 0.

[0252] In further embodiments, q is 1.

[0253] In further embodiments, Z is an oxygen atom.

[0254] In further embodiments, R3is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar-oxy-C1-6-alk(en / yn)yl, Ar—C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl and —NR12R12′; with the proviso that when R3is NR12R12′then q is 0.

[0255] In further embodiments, R3is NR12R12′, q is 0 and R12and R12′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, Ar and Ar—C1-6- alk(en / yn)yl, or R12and R12′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring which optionally contains 1, 2 or 3 further heteroatoms.

[0256] In further embodiments, each R5is independently selected from the group consisting of C1-6-alk(en / yn)yl, Ar, Ar-thio, Ar-oxy, halogen and halo-C1-6-alk(en / yn)yl or two adjacent R5together with the aromatic group to which they are attached form a 4-8 membered ring which optionally contains one or two heteroatoms.

[0257] 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- dimethylbutyramide; N-[4-Chloro-1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5- yl]-3,3-dimethylbutyramide; [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]- benzamide; N-[1-(4-Fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutyramide; 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-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- amide; [1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-carbamic acid 2- benzyloxyethyl ester; 3-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-1- methyl-1-propylurea; [1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- carbamic acid tert-butyl ester; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5- yl]-C-phenyl-methanesulfonamide; Butane-1-sulfonic acid [1-(5-chlorothiophen-2-ylmethyl)- 2,3-dihydro-1H-indol-5-yl]-amide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H- indol-5-yl]-4-fluorobenzamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropionamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol- 5-yl]-2-phenoxyacetamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- 3,3-dimethylbutyramide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- butyramide; Cyclopentanecarboxylic acid [1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H- indol-5-yl]-amide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2- thiophen-2-ylacetamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- isonicotinamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-4- dimethylaminobenzamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- 2-(4-fluorophenyl)-acetamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5- yl]-6-trifluoromethylnicotinamide; 1-tert-Butyl-3-[1-(5-chlorothiophen-2-ylmethyl)-2,3- dihydro-1H-indol-5-yl]-urea; 1-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5- yl]-3-ethyl urea; 1-Benzyl-3-[1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]- urea; 1-[1-(5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-phenethyl urea; 1-[1- (5-Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-thiophen-2-ylurea; 1-[1-(5- Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3-thiophen-3-ylurea; [1-(5- Chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-carbamic acid propyl ester; 2,2- Dimethyl-N-[6-nitro-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-propionamide; N-[1-(5-Chlorothiophen-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]-acetamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-6-nitro-2,3-dihydro- 1H-indol-5-yl]-2-(4-fluorophenyl)-acetamide; N-[1-(5-Chlorothiophen-2-ylmethyl)-6-nitro- 2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutyramide; N-[6-Amino-1-(5-chlorothiophen-2- ylmethyl)-2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutyramide; N-[6-Amino-1-(4- trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropionamide; N-[6-Amino- 1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-2,2-dimethylpropionamide; 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- dimethylbutyramide, N-[6-Amino-1-(4-fluorobenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3- dimethylbutyramide; N-[6-Amino-1-(3-fluoro-4-trifluoromethylbenzyl)-2,3-dihydro-1H- indol-5-yl]-3,3-dimethylbutyramide; N-[1-(5-Chlorothiophen-2-ylmethyl)-1H-indol-5-yl]- 3,3-dimethylbutyramide; N-[6-Bromo-1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5- yl]-3,3-dimethylbutyramide; N-[6-Bromo-1-(5-chlorothiophen-2-ylmethyl)-2,3-dihydro-1H- indol-5-yl]-3,3-dimethylbutyramide; N-[1-(4-Chlorobenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3- dimethylbutyramide; 3,3-Dimethyl-N-[1-(4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; N-[1-(4-Isopropylbenzyl)-2,3-dihydro-1H-indol-5-yl]-3,3- dimethylbutyramide; N-[1-(3-Fluoro-4-trifluoromethylbenzyl)-2,3-dihydro-1H-indol-5-yl]- 3,3-dimethylbutyramide; N-[1-(6-Chlorobenzo[1,3]dioxol-5-ylmethyl)-2,3-dihydro-1H-indol- 5-yl]-3,3-dimethylbutyramide, N-[1-(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-ylmethyl)-2,3- dihydro-1H-indol-5-yl]-3,3-dimethylbutyramide; N-[1-(2-Chloro-5-trifluoromethylbenzyl)- 2,3-dihydro-1H-indol-5-yl]-3,3-dimethylbutyramide; N-{1-[5-(4-Chlorophenoxy)-1,3- dimethyl-1H-pyrazol-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-3,3-dimethylbutyramide; 3,3- Dimethyl-N-[1-(6-p-tolyloxy-pyridin-3-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide; N-{1-[6-(4-Chlorophenyl sulfanyl)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol-5-yl}-3,3- dimethylbutyramide, N-{1-[6-(4-Cyanophenoxy)-pyridin-3-ylmethyl]-2,3-dihydro-1H-indol- 5-yl}-3,3-dimethylbutyramide; 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]thiophen-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-isoxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-butyramide, N-(1- Benzo[b]thiophen-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-methyl thiophen-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-Chlorobenzyl)-2,3-dihydro-1H-indol-5-yl]-2-(4-fluorophenyl)- acetamide; 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]dioxol-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-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. Formula 13

[0258] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 13. Such compounds are described in International Publication No. WO2009015667A1, published February 5, 2009, and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No.12 / 671,505 filed July 31, 2008; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 13, these references incorporated by reference herein control.

[0259] In an embodiment, the Kv7 channel activator is a compound according to formula 13. Formula 13wherein: 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, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy; R2 is selected from the group consisting of halogen, cyano, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, C3-8- cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, optionally substituted phenyl and optionally substituted pyridyl; wherein the phenyl and pyridyl are optionally substituted with one or more substituents independently being halogen, C1-6-alk(en / yr)yl, C3-8- cycloalk(en)yl or C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; R3 is selected from the group consisting of C1-10-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl,Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8-cycloalk(en)yl-C1-6-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 the free base or a salt thereof.

[0260] 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; 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; (2,6-Dimethyl-4-morpholin-4-yl- phenyl)-carbamic acid benzyl ester; (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-naphthalen-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)-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; Pentanoic acid (2,6-dimethyl-4-morpholin-4-yl-phenyl)-amide; 4-Methyl- pentanoic 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-pentanoic 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- pentanoic 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-butyramide; 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 the free base or a pharmaceutically acceptable salt thereof. Formula 14

[0261] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 14. Such compounds are described in International Publication No. WO2009015667A1, published February 5, 2008 and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; International Publication No. WO2006029623A1, published March 23, 2006 and corresponding to International Application No. PCT / DK2005 / 000560 filed September 2, 2005; US Patent No.7,601,870, issued October 13, 2009 and corresponding to US Application No.11 / 312,664 filed December 20, 2005; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No. 12 / 671,505 filed July 31, 2008; which are incorporated by reference in their entirety herein.In the case of any conflict of terminology in the context of Formula 14, these references incorporated by reference herein control.

[0262] In an embodiment, the Kv7 channel activator is a compound according to formula 14: Formula 14wherein, Z is O or S; q is 0 or 1; each of R1and R2is independently selected from the group consisting of halogen, cyano, amino, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, C3-8-heterocycloalk(en)yl, Aryl, Heteroaryl, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6- alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, and C3-8- heterocycloalk(en)yloxy; R3is selected from the group consisting of C1-8-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl-C1-6-alk(en / yn)yl, Aryl-C3-8- cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C3-8-heterocycloalk(en)yl-C1-6- alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8-heterocycloalk(en)yl-C1-6-alk(en / yn)yl, Heteroaryl-C alk(en / yn)yl, Heteroaryl-C3-8-cycloalk(en)yl, Heteroaryl-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, amino-C1-6-alk(en / yn)yl, amino-C3-8-cycloalk(en)yl, amino-C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl and halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; and R4is selected from the group consisting of halogen, cyano, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C3-8-heterocycloalk(en)yl, Aryl, Heteroaryl, Aryl-C1-6-alk(en / yn)yl, Aryl-C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Aryl-C3-8-heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl-C3-8-heterocycloalk(en)yl- C1-6-alk(en / yn)yl, NR5R6and R7NH—C1-6-alk(en / yn)yl; wherein: R5and R6are independently selected from the group consisting of hydrogen, Aryl-C1-6-alk(en / yn)yl, Aryl-C3-8- cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Heteroaryl-C1-6-alk(en / yn)yl, Heteroaryl-C3-8-cycloalk(en)yl and Heteroaryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, with the proviso that R5and R6are not hydrogen at the same time; and R7is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl,Aryl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Aryl-C1-6-alk(en / yn)yl, Aryl-C3-8-cycloalk(en)yl and Heteroaryl; or a pharmaceutically acceptable salt thereof.

[0263] 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-dichloro-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; Pentanoic 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; 2-Bicyclo[2.2.1]kept-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-Cyclopentyl-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-dimethyl phenyl)-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- dimethylphenyl}-acetamide; 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.

[0264] In further embodiments, Z is O or S; q is 0; R1and R2are each independently selected from the group consisting of halogen, cyano, amino, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy; R3is selected from the group consisting of C1-8- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl-C1-6- alk(en / yn)yl, Aryl-C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, amino-C1-6-alk(en / yn)yl, amino-C3-8-cycloalk(en)yl, amino-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl and halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; and R4is selected from the group consisting of halogen, cyano, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl, Aryl-C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, NR5R6and R7NH—C1-6-alk(en / yn)yl; wherein: R5and R6are each independently selected from the group consisting of hydrogen, Aryl-C1-6-alk(en / yn)yl, Aryl- C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, and C3-8-cycloalk(en)yl-C1-6alk(en / yn)yl, with the proviso that R5and R6can not both be hydrogen; and R7is selected from the group consisting of C1-6-alk(en / yn)yl; C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl-C1-6-alk(en / yn)yl, and Aryl- C3-8-cycloalk(en)yl; with the 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.

[0265] In further embodiments, R1and R2are each independently selected from the group consisting of halogen, amino, C1-6-alk(en / yn)yl, Aryl, and halo-C1-6-alk(en / yn)yl.

[0266] In further embodiments, R3is selected from the group consisting of C1-8-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl-C1-6-alk(en / yn)yl, Aryl-C3-8- cycloalk(en)yl, and amino-C1-6-alk(en / yn)yl.

[0267] In further embodiments, R4is selected from the group consisting of halogen, C1-6- alk(en / yn)yl, NR5R6and R7NH—C1-6-alk(en / yn)yl, wherein R5, R6and R7are as previously defined.

[0268] In further embodiments, R4is NR5R6, wherein R5and R6are independently selected from the group consisting of hydrogen, Aryl-C1-6-alk(en / yn)yl, and C1-6-alk(en / yn)yl, with the proviso that R5and R6cannot both be hydrogen.

[0269] In further embodiments, R4is R7NH—C1-6-alk(en / yn)yl, wherein R7is Aryl.

[0270] In further embodiments, any Aryl is optionally substituted with one or more substituents independently selected from the group consisting of amino, halogen, cyano, C1-6- alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, hydroxy, C1-6-alk(en / yn)yloxy, halo-C1-6- alk(en / yn)yloxy, di-(C1-6-alk(en / yn)yl)amino, C1-6-alk(en / yn)yl-CO—NH— and C1-6- alk(en / yn)yl-sulfonamide; or two adjacent substituents may together with the Aryl group to which they are attached form a 4-8 membered ring, which is optionally substituted with one or more C1-6-alk(en / yn)yl groups.

[0271] In further embodiments, the Kv7 channel activator is a compound according to formula 14, wherein: Z is O or S; q is 0; R1and R2are each independently selected from the group consisting of halogen, cyano, amino, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo- C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, and C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yloxy; R3is selected from the group consisting of C1-8-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl-C1-6- alk(en / yn)yl, Aryl-C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, amino-C1-6-alk(en / yn)yl, amino-C3-8-cycloalk(en)yl, amino-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl and halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; and R4is selected from the group consisting of halogen, cyano, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl, Aryl-C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, NR5R6and R7NH—C1-6-alk(en / yn)yl; wherein: R5and R6are each independently selected from the group consisting of hydrogen, Aryl-C1-6-alk(en / yn)yl, Aryl- C3-8-cycloalk(en)yl, Aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, with the proviso that R5and R6cannot both be hydrogen; and R7is selected from the group consisting of C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl, halo-C1-6-alk(en / yn)yl, halo- C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Aryl-C1-6-alk(en / yn)yl, and Aryl-C3-8-cycloalk(en)yl; with the 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. Formula 15

[0272] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 15. Such compounds are described in International Publication No. WO2009015667A1, published February 5, 2009 and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; International Publication No. WO2006092143A1, published September 8, 2006 and corresponding to International Application No. PCT / DK2006 / 000123 filed March 2, 2006; US Patent No.7,812,020, issued October 12, 2010 and corresponding to US Application No. 11 / 817,340 filed March 2, 2006; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No.12 / 671,505 filed July 31, 2008; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 15, these references incorporated by reference herein control.

[0273] In an embodiment, the Kv7 channel activator is a compound according to formula 15:Formula 15wherein, q is 0 or 1; each of R1and R2is independently selected from the group consisting of halogen, cyano, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy; and R3is selected from the group consisting of C1-8-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, optionally substituted Aryl-C1-6-alk(en / yn)yl, optionally substituted Aryl-C3-8-cycloalk(en)yl, optionally substituted Aryl-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8-heterocycloalk(en)yl-C1-6-alk(en / yn)yl, C3-8- heterocycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl, C3-8-heterocycloalk(en)yl-C1-6- alk(en / yn)yl, Heteroaryl-C1-6-alk(en / yn)yl, Heteroaryl-C3-8-cycloalk(en)yl, Heteroaryl-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, NR4R5—C1-6-alk(en / yn)yl, NR4R5—C3-8-cycloalk(en)yl NR4R5—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy-C1-6- alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl and halo-C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl; wherein each of R4and R5is independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl; as the free base or a pharmaceutically acceptable salt thereof.

[0274] 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)-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)- 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-naphthalen-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]kept-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-cyclopentylacetamide; N-(2-Chloro-4-methoxy-6-morpholin-4-yl-pyridin-3-yl)-2- cyclopentylacetamide; N-(2-Chloro-4-methoxy-6-morpholin-4-yl-pyridin-3-yl)-3,3- dimethylbutyramide; N-(4-Chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-3,3- dimethylbutyramide; N-(4-Chloro-2-methoxy-6-morpholin-4-yl-pyridin-3-yl)-propionamide; and pharmaceutically acceptable salts thereof.

[0275] In further embodiments, q is 0 or 1; R1and R2each is independently selected from the group consisting of halogen, cyano, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy; and R3is selected from the group consisting of C1-8- alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, optionally substituted aryl-C1-6-alk(en / yn)yl, optionally substituted aryl-C3-8-cycloalk(en)yl, optionally substituted aryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8-heterocycloalk(en)yl-C1-6- alk(en / yn)yl, C3-8-heterocycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8- heterocycloalk(en)yl-C1-6-alk(en / yn)yl, heteroaryl-C1-6-alk(en / yn)yl, heteroaryl-C3-8- cycloalk(en)yl, heteroaryl-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, NR4R5—C1-6-alk(en / yn)yl, NR4R5—C3-8-cycloalk(en)yl, NR4R5—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6- alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl and halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, wherein: R4and R5each is independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl. Formula 16

[0276] In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 16. Such compounds are described in International Publication No. WO2009015667A1, published February 5, 2009 and corresponding to International Application No. PCT / DK2008 / 050191 filed July 31, 2008; US Publication No. US20100256145A1, published October 7, 2010 and corresponding to US Application No.12 / 671,505 filed July 31, 2008; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 16, these references incorporated by reference herein control.

[0277] In an embodiment, the Kv7 channel activator is a compound according to formula 16: Formula 16wherein: q is 0 or 1; R1and R2are independently selected from the group consisting of hydrogen and optionally substituted aryl-C1-6-alk(en / yn)yl, provided that R1and R2are not both hydrogen; or R1and R2together with the nitrogen to which they are attached form a 5 to 7 membered ring optionally containing a further heteroatom; R2and R4are independently selected from hydrogen, halogen, cyano, amino, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, halo- C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, halo-C1-6-alk(en / yn)yloxy, halo-C3-8-cycloalk(en)yloxy and halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, provided that R3and R4are not both hydrogen; and R5is selected from the group consisting of C1-10-alk(en / yn)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, optionally substituted aryl-C1-6-alk(en / yn)yl and optionally substituted aryl; as the free base or a pharmaceutically acceptable salt thereof.

[0278] 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- cyclopentylacetamide; N-[4-Amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5- yl]-3,3-dimethylbutyramide; 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-dimethylbutyramide; 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 the free base or a pharmaceutically acceptable salt thereof. Formula 17 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 17. Such compounds are described in International Publication No. WO2007065449A1, published June 14, 2007 and corresponding to International Application No. PCT / DK2006 / 050039 filed September 7, 2006; which is incorporated by reference in its entirety herein. In the case of any conflict of terminology in the context of Formula 17, this reference incorporated by reference herein controls.

[0279] In an embodiment, the Kv7 channel activator is a compound according to formula 17:Formula 17, wherein: q is 0 or 1; R1and R2are independently selected from the group consisting of hydrogen and optionally substituted aryl-C1-6-alk(en / yn)yl, provided that R1and R2are not both hydrogen, or R1and R2together with the nitrogen to which they are attached form a 5 to 7 membered ring optionally containing a further heteroatom;R3and R4are independently selected from hydrogen, halogen, cyano, amino, C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, halo- C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, halo-C1-6-alk(en / yn)yloxy, halo-C3-8-cycloalk(en)yloxy and halo-C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yloxy, provided that R3and R4are not both hydrogen;R5is selected from the group consisting of C1-10-alk(en / yn)yl, C3-8-cycloalk(en)yl- C1-6- alk(en / yn)yl, optionally substituted aryl-C1-6-alk(en / yn)yl and optionally substituted aryl; as the free base or salts thereof.

[0280] In further embodiments, q is 0.

[0281] In further embodiments, q is 1.

[0282] In further embodiments, R1and R2are independently selected from hydrogen and optionally substituted aryl-C1-6-alk(en / yn)yl, provided that R1and R2are not both hydrogen.

[0283] In further embodiments, R1and R2together with the nitrogen to which they are attached form a 5 to 7 membered ring optionally containing a further hetero atom.

[0284] In further embodiments, said further hetero atom is oxygen.

[0285] In further embodiments, said ring is a 6 membered ring.

[0286] In further embodiments, said ring is a morpholine ring.

[0287] In further embodiments, R3and R4are independently selected from amino and C1-6- alk(en / yn)yl, preferably methyl.

[0288] In further embodiments, R5is selected from the group consisting of C1-10-alk(en / yn)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, optionally substituted aryl-C1-6-alk(en / yn)yl and optionally substituted aryl.

[0289] 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- cyclopentylacetamide, N-[4-Amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-3,3- dimethylbutyramide, 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-moφholin-4-yl-pyrimidin-5-yl)-acetamide, N-(4,6-Dimethyl-2-moφholin- 4-yl-pyrimidin-5-yl)-3,3-dimethylbutyramide, N-(4,6-Dimethyl-2-moφholin-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-moφholin-4-ylpyrimidin-5-yl)-2-(3- fluorophenyl)-acetamide and Hexanoic acid (4,6-dimethyl-2-moφholin-4-ylpyrimidin-5-yl)- amide; as the free base or a salt thereof. Formula 18 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 18. Such compounds are described in International Publication No. WO2004096767A1, published November 11, 2004 and corresponding to International Application No. PCT / DK2004 / 000283 filed April 23, 2004; US Publication No. US20060264496A1, published November 23, 2006 and corresponding to US Application No. 10 / 551,783 filed April 23, 2004; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 18, these references incorporated by reference herein control.

[0290] In an embodiment, the Kv7 channel activator is a compound according to formula 18: Formula 18, wherein, the dotted line represents an optional bond; R1and R1′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R1and R1′together with the carbon atom to which they are attached form a 3-8 membered saturated or unsaturated ring which optionally contains 1 or 2 heteroatoms; s is 0 or 1; U is O, NR11, S, SO2, SO2NR11, CO—O or CO—NR11; wherein R11is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; or R2and R11together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring which optionally contains 1, 2 or 3 further heteroatoms; R2is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar— C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, acyl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8- cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halogen, halo-C1-6- alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, —NO2, NR10R10′—C1-6-alk(en / yn)yl, NR10R10′—C3-8-cycloalk(en)yl and NR10R10′—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein R10and R10′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8- cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, or R10and R10′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring which optionally contains 1, 2 or 3 further heteroatoms; with the proviso that when R2is NO2, halogen or cyano then s is 0; and with the proviso that when R2is a hydrogen atom or acyl and s is 1 then U is NR11, O or S; wherein the group —(U)s—R2is linked to position 4 or 6 of the indole or indoline; q is 0 or 1; Z is O or S; X is CO or SO2; with the proviso that q is 0 when X is SO2; R3is selected from the group consisting of C1-6- alk(en / yn)yl, C3-8-cycloalk(en)yl, heterocycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yl-heterocycloalk(en)yl, Ar, Ar—C1-6- alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar-heterocycloalk(en)yl, Ar—C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar—C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, Ar—C1-6-alk(en / yn)yl- heterocycloalk(en)yl, C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-C1-6- alk(en / yn)yl, C1-6-alk(en / yn)yloxy-C3-8-cycloalk(en)yl, C1-6-alk(en / yn)yloxy- heterocycloalk(en)yl, Ar-oxy-C1-6-alk(en / yn)yl, Ar—C1-6-alk(en / yn)yloxy-C1-6-alk(en / yn)yl, C1-6-alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yloxy-carbonyl-C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy-carbonyl-C1-6-alk(en / yn)yl, hydroxy- C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-heterocycloalk(en)yl, hydroxy-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, hydroxy-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo- heterocycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl-C3-8- cycloalk(en)yl, halo-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, halo-C1-6-alk(en / yn)yl-Ar, halo- C3-8-cycloalk(en)yl-Ar, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl-Ar, halo-C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl-Ar, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano- heterocycloalk(en)yl, cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl- C3-8-cycloalk(en)yl, cyano-C1-6-alk(en / yn)yl-heterocycloalk(en)yl, acyl-C1-6-alk(en / yn)yl, acyl-C3-8-cycloalk(en)yl, acyl-heterocycloalk(en)yl, acyl-C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, acyl-C1-6-alk(en / yn)yl-C3-8-cycloalk(en)yl, acyl-C1-6-alk(en / yn)yl- heterocycloalk(en)yl and —NR12R12′, optionally substituted NR12R12′—C1-6-alk(en / yn)yl, optionally substituted NR12R12′—C3-8-cycloalk(en)yl, optionally substituted NR12R12′—C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl; wherein R12and R12′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6- alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar—C3-8-cycloalk(en)yl, Ar—C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl, hydroxy-C1-6-alk(en / yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, or R12and R12′together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring which optionally contains 1, 2 or 3 further heteroatoms; with the proviso that when R3is NR12R12′then q is 0; and Y is selected from the groups according to the following formulas:, 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; with the proviso 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 R5is independently selected from the group consisting of a C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar, Ar—C1-6-alk(en / yn)yl, Ar-thio, Ar-oxy, acyl, C1-6- alk(en / yn)yloxy, C3-8-cycloalk(en)yloxy, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yloxy, halogen, halo-C1-6-alk(en / yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, —CO—NR6R6′, cyano, cyano-C1-6-alk(en / yn)yl, cyano-C3-8-cycloalk(en)yl, cyano-C3-8- cycloalk(en)yl-C1-6-alk(en / yn)yl, —NR7R7′, —S—R8and —SO2R8, or two adjacent R5together with the aromatic group to which they are attached form a 4-8 membered ring which optionally contains one or two heteroatoms; R6and R6′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl- C1-6-alk(en / yn)yl and Ar; R7and R7′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Arand acyl; and R8is selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl, Ar and —NR9R9′; wherein R9and R9′are independently selected from the group consisting of hydrogen, C1-6-alk(en / yn)yl, C3-8- cycloalk(en)yl and C3-8-cycloalk(en)yl-C1-6-alk(en / yn)yl; provided that when R8is — NR9R9′then R5is not —S—R8; or salts thereof. Formula 19 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 19. Such compounds are described in US Patent No. 9,248,122, issued February 2, 2016 and corresponding to US Application No.14 / 091,395 filed November 27, 2013; which is incorporated by reference in its entirety herein. In the case of any conflict of terminology in the context of Formula 19, this reference incorporated by reference herein controls.

[0291] In an embodiment, the Kv7 channel activator is a compound according to formula 19: Formula 19wherein, A1, A2and A3independently of each other represent CR4, N, O, S or N(CH3), A4represents CR4or N, and n denotes 0 or 1, with the proviso, that at least one of A1, A2, A3and A4does not represent CR4, and with the proviso, that if n denotes 0, then precisely one of A1, A2and A3represents O, S or N(CH3), or if n denotes 1, then A1, A2and A3independently of each other represent CR4or N, R1represents C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; R2represents F; Cl; Br; I; CN; CF3; C(═O)H; NO2; OCF3; SCF3; C1-4-aliphatic residue, C(═O)—C1-4-aliphatic residue, C(═O)— O—C1-4-aliphatic residue, C(═O)—NH—C1-4-aliphatic residue, C(═O)—N(C1-4-aliphatic residue)2, O—C1-4-aliphatic residue, O—C(═O)—C1-4-aliphatic residue, S—C1-4-aliphaticresidue, S(═O)2—C1-4-aliphatic residue, S(═O)2—O—C1-4-aliphatic residue, wherein the C1-4-aliphatic residue may be in each case be unsubstituted or mono- or polysubstituted; C3-6- cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4- aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; R3represents C2-10-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-10- cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-8- aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, or denotes S—R5, O—R6or N(R7R8), wherein R5and R6in each case represent C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; with the proviso, that if R5or R6denote a 3 to 10 membered heterocycloaliphatic residue, than the 3 to 10 membered heterocycloaliphatic residue is linked via a carbon atom, R7represents C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; with the proviso that if R7denotes 3 to 10 membered heterocycloaliphatic residue, the 3 to 10 membered heterocycloaliphatic residue is linked via a carbon atom; and R8denotes C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; or R7and R8form together with the nitrogen atom connecting them a 3 to 10 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted; and each R4independently represents H, F; Cl; Br; I; CN; CF3; CHF2; CH2F; OCF3; OCHF2; OCH2F; SCF3; O—C1-4-aliphatic residue, C1-4-aliphatic residue or S(═O)2—C1-4-aliphatic residue; in which an “aliphatic group” and “aliphatic residue” may in each case be branched or unbranched, saturated or unsaturated, in which a “cycloaliphatic residue” and a “heterocycloaliphatic residue” may in each case be saturated or unsaturated, in which “mono- or polysubstituted” with respect to an “aliphatic group”, an “aliphatic residue”, a “cycloaliphatic residue” and a “heterocycloaliphatic residue” relates, with respect to the corresponding residues or groups, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, NH—C(═O)—C1-4aliphatic residue, N(C1-4aliphatic residue)-C(═O)—C1-4aliphatic residue, NH—S(═O)2— C1-4aliphatic residue, N(C1-4aliphatic residue)-S(═O)2—C1-4aliphatic residue, ═O, OH, OCF3, O—C1-4-aliphatic residue, O—C(═O)—C1-4-aliphatic residue, SH, SCF3, S—C1-4- aliphatic residue, S(═O)2OH, S(═O)2—C1-4-aliphatic residue, S(═O)2—O—C1-4-aliphatic residue, S(═O)2—NH(C1-4-aliphatic residue), S(═O)2—N(C1-4-aliphatic residue)2, CN, CF3, CHO, COOH, C1-4-aliphatic residue, C(═O)—C1-4-aliphatic residue, C(═O)—O—C1-4- aliphatic residue, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, C(═O)NH2, a C(═O)—NH(C1-4-aliphatic residue) and C(═O)—N(C1-4-aliphatic residue)2; in which “mono- or polysubstituted” with respect to “aryl” and a “heteroaryl” relates, with respect to the corresponding residues, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2,NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, NH—C(═O)—C1-4-aliphatic residue, N(C1-4aliphatic residue)- C(═O)—C1-4aliphatic residue, NH—S(═O)2—C1-4aliphatic residue, N(C1-4aliphatic residue)-S(═O)2—C1-4aliphatic residue, OH, OCF3, O—C1-4-aliphatic residue, O—C(═O)— C1-4-aliphatic residue, SH, SCF3, S—C1-4-aliphatic residue, S(═O)2OH, S(═O)2—C1-4- aliphatic residue, S(═O)2—O—C1-4-aliphatic residue, S(═O)2—NH(C1-4-aliphatic residue), S(═O)2—N(C1-4-aliphatic residue)2, CN, CF3, C(═O)H, C(═O)OH, C1-4-aliphatic residue, C(═O)—C1-4-aliphatic residue, C(═O)—O—C1-4-aliphatic residue, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, benzyl, aryl, heteroaryl, C(═O)NH2, C(═O)—NH(C1-4-aliphatic residue) and C(═O)—N(C1-4-aliphatic residue)2; in the form of an individual single stereoisomer or a mixture of the stereoisomers in any mixing ratio, and / or in the form of a free compound, a solvate and / or a physiologically acceptable salt.

[0292] In further embodiments, A1, A2and A3independently of each other represent CR4, N, O, S or N(CH3), A4represents CR4or N, and n denotes 0 or 1, with the proviso, that at least one of A1, A2, A3and A4does not represent CR4, and with the proviso, that if n denotes 0, then precisely one of A1, A2and A3represents O, S or N(CH3), or if n denotes 1, then A1, A2and A3independently of each other represent CR4or N, R1denotes C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each casemay be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, or denotes C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)—OH, C3-8-cycloaliphatic residue and 3 to 7 membered heterocycloaliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-8-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the C3-10- cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, or denotes aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, O3-8-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue,benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I,NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4-aliphatic residue, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the aryl or the heteroaryl residue may in each case be optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN and C(═O)OH, R2represents F; Cl; Br; I; CN; CF3; NO2; OCF3; SCF3; C1-4-aliphatic residue, S—C1-4-aliphatic residue, O—C1-4-aliphatic residue, wherein the C1-4-aliphatic residue may be in each case be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, Or C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4- aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4- aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN and C(═O)OH, R3denotes C2-10-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, Or denotes C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-10-cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, Or denotes S—R5, O—R6or N(R7R8), wherein R5and R6in each case represent C1-10- aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4- aliphatic residue, or in each case represent C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4- aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)—OH, C3-8- cycloaliphatic residue and 3 to 7 membered heterocycloaliphatic residue, wherein the C1-4- aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-8-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the C3-10-cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a C1-8-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, on the condition that if R5or R6denote a 3 to 10 membered heterocycloaliphatic residue, the 3 to 10 membered heterocycloaliphatic residue is linked via a carbon atom, R7denotes a C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)—O—C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and an unsubstituted O—C1-4-aliphatic residue, or denotes a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)—O—C1-4-aliphatic residue, C3-6-cycloaliphatic residue and 3 to 7 membered heterocycloaliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the C3-10- cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a O1-0-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, C(═O)—O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, on the condition that if R7denotes a 3 to 10 membered heterocycloaliphatic residue, the 3 to 10 membered heterocycloaliphatic residue is linked via a carbon atom, and / orR8denotes C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4- aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, Or R7and R8form together with the nitrogen atom connecting them a 3 to 10 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)—OH, C3-6-cycloaliphatic residue and 3 to 7 membered heterocycloaliphatic residue,wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, And / or wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the 3 to 10 membered heterocycloaliphatic residue formed by R7and R8together with the nitrogen atom connecting them may optionally be condensed with aryl or heteroaryl, wherein the aryl or heteroaryl residues condensed in this way can for their part be respectively unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4- aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue,benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl andoxazolyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4-aliphatic residue, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, and wherein the C3-6cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)—OH, and each R4independently represents H, F, Cl, Br, I, CN, CF3, CHF2, CH2F, OCF3, OCHF2, OCH2F, SCF3, O—C1-4-aliphatic residue, C1-4-aliphatic residue or S(═O)2—C1-4-aliphatic residue. In further embodiments, n denotes 1 and A1represents N, A2represents CR4, A3represents CR4and A4represents CR4; or n denotes 1 and A1represents CR4, A2represents N, A3represents CR4and A4represents CR4; or n denotes 1 and A1represents CR4, A2represents CR4, A3represents N and A4represents CR4; or n denotes 1 and A1represents CR4, A2represents CR4, A3represents CR4and A4represents N; or n denotes 1 and A1represents N, A2represents N, A3represents CR4and A4represents CR4; or n denotes 1 and A1represents N, A2represents CR4, A3represents N and A4represents CR4; or n denotes 1 and A1represents N, A2represents CR4, A3represents CR4and A4represents N; or n denotes 1 and A1represents CR4, A2represents N, A3represents N and A4represents CR4; or n denotes 1 and A1represents CR4, A2represents N, A3represents CR4and A4represents N; or n denotes 1 and A1represents CR4, A2represents CR4, A3represents N and A4represents N; or n denotes 0 and A1represents CR4, A2represents CR4, and A3represents S; or n denotes 0 and A1represents N, A2represents CR4, and A3represents S; or n denotes 0 and A1represents S, A2represents CR4and A3represents CR4; or n denotes 0 and A1represents S, A2represents CR4and A3represents N.

[0293] In further embodiments, R2represents F; Cl; Br; I; CN; CF3; NO2; OCF3; SCF3; C1-4- aliphatic residue, S—C1-4-aliphatic residue or O—C1-4-aliphatic residue, wherein the C1-4- aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at leastone substituent selected from the group consisting of F, Cl, Br, I, ═O, OH and O—C1-4- aliphatic residue.

[0294] In further embodiments, R2represents C1-4-aliphatic residue.

[0295] In further embodiments, each R4independently represents H; F; Cl; Br; CN; CF3; OCF3; CH3, OCH3or S(═O)2CH3.

[0296] In further embodiments, R1represents the partial structure:wherein, m denotes 0, 1, or 2, R1aand R1beach independently of one another represent H, F, Cl, Br, I, O—C1-4-aliphatic residue or C1-4-aliphatic residue, R1cdenotes C1-4-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, O—C1-4-aliphatic residue, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, CF3and O—C1-4-aliphatic residue, or denotes C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, O—C1-4-aliphatic residue, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, CF3and O—C1-4-aliphatic residue, or denotes aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C1-4-aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, benzyl, phenyl, thienyl or pyridyl, wherein benzyl, phenyl, thienyl and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C1-4-aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, and wherein the C3-6cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selectedfrom the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, CF3C1-4- aliphatic residue and C(═O)OH.

[0297] In further embodiments, m denotes 1 or 2, R1aand R1brepresent H, R1cdenotes C1-4- aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, O—C1-4-aliphatic residue, CF3and C1-4- aliphatic residue, or denotes C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, O—C1-4-aliphatic residue, CF3and C1-4-aliphatic residue, or m denotes 0 and R1cdenotes aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C1-4-aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, benzyl, phenyl, thienyl or pyridyl, wherein benzyl, phenyl, thienyl and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C1-4-aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, CF3, C1-4-aliphatic residue and C(═O)OH.

[0298] In further embodiments, R3denotes a C2-6-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN and C1-4-aliphatic residue wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, CF3and O—C1-4-aliphatic residue, or denotes C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, (═O)—O—C1-4-aliphatic residue, S—C1-4- aliphatic residue, CF3, CN and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-7-cycloaliphatic residue or the 3 to 7 memberedheterocycloaliphatic residue may in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN and C1-4-aliphatic residue, or R3denotes S—R5or O—R6, wherein R5and R6in each case denote C1-8-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, NH(C1-4-aliphatic residue), N(C1-4- aliphatic residue)2, CF3and C1-4-aliphatic residue wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, CF3and O—C1-4-aliphatic residue, or in each case denote C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue may be linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, CF3, CN and C1-4-aliphatic residue, on the condition that if R5or R6denotes 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, or R3denotes N(R7R8), wherein R7denotes C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, or denotes C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue may in each case be linked, via a C1-4-aliphatic group, which in turn may beunsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN and C1-4-aliphatic residue, on the condition that if R7denotes 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, and R8denotes C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, or R7and R8form together with the nitrogen atom connecting them a 3 to 10 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, CF3and O—C1-4-aliphatic residue, and wherein the 3 to 10 membered heterocycloaliphatic residue formed by R7and R8together with the nitrogen atom connecting them may optionally be condensed with aryl or heteroaryl, wherein the aryl or heteroaryl residues condensed in this way can for their part be respectively unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, ON, C1-4-aliphatic residue, C(═O)OH, C3-6cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue,benzyl, phenyl, thienyl, and pyridyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, thienyl, and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, O—C1-4-aliphatic residue, OCF3, OCH2CH2OH, OCH2OCH3, SCF3, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue and C(═O)OH.

[0299] In further embodiments, R3denotes C2-6-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, or denotes C3-6- cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4- aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with OH or O—C1-4-aliphatic residue, and wherein the C3-6- cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue may in each case optionally linked via a C1-4-aliphatic group, or R3denotes S—R5or O—R6, wherein R5and R6in each case denote C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4- aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, or in each case denote C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue in each case may be linked via an unsubstituted C1-4-aliphatic group, on the condition that if R5or R6denotes 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, or R3denotes N(R7R8), wherein R7denotes C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, or denotes C3-6- cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4- aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted ormono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue is in each case linked via a unsubstituted C1-4-aliphatic group, on the condition that if R7denotes 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, and R8denotes unsubstituted C1-4-aliphatic residue, or R7and R8form together with the nitrogen atom connecting them a 3 to 7 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, and wherein the 3 to 7 membered heterocycloaliphatic residue formed by R7and R8together with the nitrogen atom connecting them may optionally be condensed with phenyl or pyridyl, wherein the phenyl or pyridyl residues condensed in this way can for their part be respectively unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN, C1-4-aliphatic residue, C(═O)OH, benzyl, phenyl, and pyridyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OCH3, OCF3, OCH2CH2OH, OCH2CH2OCH3, SCF3, CF3and C1-4-aliphatic residue.

[0300] In further embodiments, A1, A2and A3independently of each other represent CR4, N, O, S or N(CH3), A4represents CR4or N, and n denotes 0 or 1, with the proviso, that at least one of A1, A2, A3and A4does not represent CR4, and with the proviso, that if n denotes 0, then precisely one of A1, A2and A3represents O, S or N(CH3), or if n denotes 1, then A1,A2and A3independently of each other represent CR4or N, R1represents the partial structure:wherein: m denotes 0, 1, or 2, R1aand R1beach independently of one another represent H, F, Cl, O—C1-4-aliphatic residue or C1-4-aliphatic residue, R1cdenotes C1-4-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, C1-10—C1-4aliphatic residue, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, CF3and O—C1-4-aliphatic residue, or denotes C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, C1-10—C1-4-aliphatic residue, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, CF3and O—C1-4-aliphatic residue, or denotes aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, O—C1-4-aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, benzyl, phenyl, thienyl or pyridyl, wherein benzyl, phenyl, thienyl and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, O—C1-4- aliphatic residue, OCF3, CF3, CN, C1-4-aliphatic residue, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, ═O, O—C1-4-aliphatic residue, OCF3, CF3C1-4-aliphatic residue and C(═O)OH, R2represents F; Cl; Br; I; CN; CF3; NO2; OCF3; SCF3; C1-4-aliphatic residue, S—C1-4- aliphatic residue or O—C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected fromthe group consisting of F, Cl, ═O, OH and O—C1-4-aliphatic residue, R3denotes C2-6- aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, or denotes C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with OH or O—C1-4-aliphatic residue, and wherein the C3-10-cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a C1-4-aliphatic group, or R3denotes S—R5or O—R6, wherein R5and R6in each case denote C1-8-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4- aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, or in each case denote C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue, wherein the C1-4- aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4- aliphatic residue, and wherein the C3-6-cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue in each case may be linked via an unsubstituted C1-4-aliphatic group, on the condition that if R5or R6denotes 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, or R3denotes N(R7R8), wherein R7denotes C1-8-aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4- aliphatic residue, OCF3, SCF3, CF3and C1-4-aliphatic residue wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4-aliphatic residue, or denotes C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, C(═O)—O—C1-4-aliphatic residue, CF3and C1-4-aliphatic residue, wherein the C1-4-aliphaticresidue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue or the 3 to 7 membered heterocycloaliphatic residue is in each case linked via an unsubstituted C1-4-aliphatic group, on the condition that if R7denotes 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, and R8denotes unsubstituted C1-4-aliphatic residue, or R7and R8form together with the nitrogen atom connecting them a 3 to 7 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, ═O, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN and C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, CF3and O—C1-4- aliphatic residue, and wherein the 3 to 7 membered heterocycloaliphatic residue formed by R7and R8together with the nitrogen atom connecting them may optionally be condensed with phenyl or pyridyl, wherein the phenyl or pyridyl residues condensed in this way can for their part be respectively unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, O—C1-4-aliphatic residue, OCF3, SCF3, CF3, CN, C1-4-aliphatic residue, C(═O)OH, benzyl, phenyl, and pyridyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OH, and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, and pyridyl, may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, OCH3, OCF3, OCH2CH2OH, O CH2CH2OCH3, SH, SCF3, CF3and C1-4-aliphatic residue; and each R4independently represents H, F, Cl, Br, CN, CF3, OCF3, CH3, OCH3or S(═O)2CH3.

[0301] In further embodiments, the Kv7 channel activator is selected from the group consisting of:12-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,5]naphthyridine-3- carboxylic acid amide; 22-Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl- [1,5]naphthyridine-3-carboxylic acid amide; 3-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4- methyl-[1,6]naphthyridine-3-carboxylic acid amide; 42-Ethylsulfanyl-N-[(4-fluorophenyl)- methyl]-4-methyl-[1,6]naphthyridine-3-carboxylic acid amide; 52-Ethylsulfanyl-N-[(3- fluorophenyl)-methyl]-4-methyl-[1,7]naphthyridine-3-carboxylic acid amide; 6- Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,7]naphthyridine-3-carboxylic acid amide; 72-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,8]naphthyridine-3-carboxylic acid amide; 82-Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl- [1,8]naphthyridine-3-carboxylic acid amide; 92-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]- 4-methyl-7-(trifluoromethyl)-[1,8]naphthyridine-3-carboxylic acid amide; 102- Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,8]naphthyridine- 3-carboxylic acid amide; 112-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7- (trifluoromethyl)-[1,6]naphthyridine-3-carboxylic acid amide; 122-Ethylsulfanyl-N-[(4- fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,6]naphthyridine-3-carboxylic acid amide; 132-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)- [1,5]naphthyridine-3-carboxylic acid amide; 142-Ethylsulfanyl-N-[(4-fluorophenyl)- methyl]-4-methyl-7-(trifluoromethyl)-[1,5]naphthyridine-3-carboxylic acid amide; 155- Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-7-methyl-thieno[3,2-b]pyridine-6-carboxylic acid amide; 166-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-thieno[2,3-b]pyridine-5- carboxylic acid amide; 175-Ethoxy-N-[(3-fluorophenyl)-methyl]-7-methyl-2- (trifluoromethyl)-thieno[3,2-b]pyridine-6-carboxylic acid amide; 186-Ethoxy-N-[(3- fluorophenyl)-methyl]-4-methyl-2-(trifluoromethyl)-thieno[2,3-b]pyridine-5-carboxylic acid amide; in the form of a free compound, a solvate and / or a physiologically acceptable salt. Formula 20 In an embodiment, the Kv7 channel activator may be selected from one of the following compounds according to Formula 20. Such compounds are described in US Patent No. 9,284,286 issued March 15, 2016 and corresponding to US Application No.14 / 091.373 filed November 27, 2013; International Publication No. WO2014082737A1, published June 5, 2014 and corresponding to International Application No. PCT / EP2013 / 003572 filed November 27, 2013; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 20, these references incorporated by reference herein control.

[0302] In an embodiment, the Kv7 channel activator is a compound according to formula 20:Formula 20wherein: A1represents CR10R11or S; A2represents CR12R13, C(═O), O, S, S(═O) or S(═O)2; A3, A4and A5independently of each other represent CR7, N, O, S or NR8, A6represents CR7or N, and n denotes 0 or 1, with the proviso, that if n denotes 0, then precisely one of A3, A4and A5represents O, S or NR8, or if n denotes 1, then A3, A4and A5independently of each other represent CR7or N; and with the proviso, that if n denotes 1 and A3, A4and A5each represent CR7, then A6does not represent N; R1represents C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; R2, R3; R4, R5, R10, R11, R12and R13each independently of another represent H; F; Cl; Br; I; NO2; CF3; CN; OH; OCF3; SH; SCF3; C1-10-aliphatic residue, O—C1-10-aliphatic residue or S—C1-10-aliphatic residue, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted; or C3-10-cycloaliphatic residue, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted; or R2and R3or R4and R5or R10and R11or R12and R13or R2and R11or R2and R4or R2and R13or R4and R13or R4and R11or R12and R13, together with the carbon atom(s) joining them, form a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case saturated or unsaturated, unsubstituted or mono- or poly-substituted; wherein the remaining substituents R2, R3; R4; R5; R10, R11, R12and R13in each case have the meaning given above; R6represents a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case saturated or unsaturated, unsubstituted or mono- or poly-substituted; or represents an aryl or a heteroaryl, in each case unsubstituted or mono- or poly-substituted; each R7independently of each otherrepresents H, F; Cl; CN; CF3; CHF2; CH2F; OCF3; OCHF2; OCH2F; SCF3; O—C1-4-aliphatic residue, C1-4-aliphatic residue or S(═O)2—C1-4-aliphatic residue, wherein the C1-4-aliphatic residue in each case may be saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted; and R8represents H or a C1-4-aliphatic residue, wherein the aliphatic residue may be saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted; in which an “aliphatic group” and “aliphatic residue” may in each case be branched or unbranched, saturated or unsaturated, in which a “cycloaliphatic residue” and a “heterocycloaliphatic residue” may in each case be saturated or unsaturated, in which “mono- or polysubstituted” with respect to an “aliphatic group”, an “aliphatic residue”, a “cycloaliphatic residue” and a “heterocycloaliphatic residue” relates, with respect to the corresponding residues or groups, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, NH—C(═O)— C1-4aliphatic residue, N(C1-4-aliphatic residue)-C(═O)—C1-4-aliphatic residue, NH— S(═O)2—C1-4-aliphatic residue, N(C1-4-aliphatic residue)-S(═O)2—C1-4-aliphatic residue, ═O, OH, OCF3, O—C1-4-aliphatic residue, O—C(═O)—C1-4-aliphatic residue, SH, SCF3, S—C1-4-aliphatic residue, S(═O)2OH, S(═O)2—C1-4-aliphatic residue, S(═O)2—O—C1-4- aliphatic residue, S(═O)2—NH(C1-4-aliphatic residue), S(═O)2—N(C1-4-aliphatic residue)2, CN, CF3, CHO, COOH, C1-4-aliphatic residue, C(═O)—C1-4-aliphatic residue, C(═O)—O— C1-4-aliphatic residue, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, benzyl, aryl, heteroaryl, C(═O)NH2, a C(═O)—NH(C1-4-aliphatic residue) and C(═O)—N(C1-4-aliphatic residue)2; in which “mono- or polysubstituted” with respect to “aryl” and a “heteroaryl” relates, with respect to the corresponding residues, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2,NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, NH—C(═O)—C1-4-aliphatic residue, N(C1-4aliphatic residue)-C(═O)—C1- 4 aliphatic residue, NH—S(═O)2—C1-4aliphatic residue, N(C1-4aliphatic residue)-S(═O)2— C1-4aliphatic residue, OH, OCF3, O—C1-4-aliphatic residue, O—C(═O)—C1-4-aliphatic residue, SH, SCF3, S—C1-4-aliphatic residue, S(═O)2OH, S(═O)2—C1-4-aliphatic residue, S(═O)2—O—C1-4-aliphatic residue, S(═O)2—NH(C1-4-aliphatic residue), S(═O)2—N(C1-4-aliphatic residue)2, CN, CF3, C(═O)H, C(═O)OH, C1-4-aliphatic residue, C(═O)—C1-4- aliphatic residue, C(═O)—O—C1-4-aliphatic residue, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, benzyl, aryl, heteroaryl, C(═O)NH2, C(═O)— NH(C1-4-aliphatic residue) and C(═O)—N(C1-4-aliphatic residue)2; in the form of an individual single stereoisomer or a mixture of the stereoisomers in any mixing ratio, and / or in the form of a free compound, a solvate and / or a physiologically acceptable salt.

[0303] In further embodiments, A1represents CR10R11or S; A2represents CR12R13, C(═O), O, S, S(═O) or S(═O)2; A3, A4and A5independently of each other represent CR7, N, O, S or NR8, A6represents CR7or N, and n denotes 0 or 1, with the proviso, that if n denotes 0, then precisely one of A3, A4and A5represents O, S or NR8, or if n denotes 1, then A3, A4and A5independently of each other represent CR7or N; and with the proviso, that if n denotes 1 and A3, A4and A5each represent CR7, then A6does not represent N; R1denotes a C1-10- aliphatic residue, unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4- aliphatic residue, or denotes a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4- aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C3-6- cycloaliphatic residue and a 3 to 7 membered heterocycloaliphatic residue, wherein the C1-4- aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the C3-10-cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case be optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituentselected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, or denotes an aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C3-6cycloaliphatic residue, 3 to 6 membered heterocycloaliphatic residue,benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4-aliphatic residue, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S— C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the aryl or the heteroaryl residue may in each case be optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN and C(═O)OH, R2, R3, R5, R10, R11, R12and R13each independently of the others represents H; F; Cl; Br; I; NO2; CF3; CN; OH; OCF3; SH; SCF3; C1-4-aliphatic residue, O—C1-4-aliphatic residue or S—C1-4-aliphatic residue, in each case saturated or unsaturated, branched or unbranched, wherein the C1-4- aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at leastone substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, or a C3-10-cycloaliphatic residue, saturated or unsaturated, branched or unbranched, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4- aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-10-cycloaliphatic residue may in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, or R2and R3or R4and R5or R10and R11or R12and R13or R2and R11or R2and R4or R2and R13or R4and R13or R4and R11or R12and R13, together with the carbon atom(s) joining them, form a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case saturated or unsaturated and in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-10-cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4- aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the remaining substituents R2, R3, R4, R5, R10, R11, R12and R13in each case have the meaning given above; R6represents a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case saturated or unsaturated and in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue,CF3, CN, C1-4-aliphatic residue, C(═O)OH, C3-6-cycloaliphatic residue and 3 to 7 membered heterocycloaliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4- aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the C3-10- cycloaliphatic residue or the 3 to 10 membered heterocycloaliphatic residue may in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, or represents an aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3, C(═O)OC2H5, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue,benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue, and wherein benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl may in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, O—C1-4- aliphatic residue, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue, C(═O)OH, C(═O)CH3, C(═O)C2H5, C(═O)OCH3and C(═O)OC2H5, and wherein the C3-6-cycloaliphatic residue and the 3 to 7 membered heterocycloaliphatic residue may in each case may be unsubstituted or mono- orpolysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN, C1-4-aliphatic residue and C(═O)OH, and wherein the aryl or the heteroaryl residue may in each case be optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, OH, ═O, O—C1-4-aliphatic residue, OCF3, SH, SCF3, S—C1-4-aliphatic residue, CF3, CN and C(═O)OH, each R7independently of each other represents H, F; Cl; CN; CF3; CHF2; CH2F; OCF3; OCHF2; OCH2F; SCF3; a O—C1-4-aliphatic residue, a C1-4-aliphatic residue or a S(═O)2—C1-4- aliphatic residue, wherein the C1-4-aliphatic residue in each case may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue. and R8represents H or C1-4-aliphatic residue, wherein the C1-4-aliphatic residue may be unsubstituted or mono- or polysubstituted with at least one substituent selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3and O—C1-4-aliphatic residue.

[0304] In further embodiments, A1represents S; and A2represents S, S(═O)2or CR12R13, wherein R12and R13both represent H or both represent F.

[0305] In further embodiments, n denotes 1 and A3represents CR7, A4represents CR7, A5represents CR7and A6represents CR7; or n denotes 1 and A3represents N, A4represents CR7, A5represents CR7and A6represents CR7; or n denotes 1 and A3represents CR7, A4represents N, A5represents CR7and A6represents CR7; or n denotes 1 and A3represents CR7, A4represents CR7, A5represents N and A6represents CR7; or n denotes 1 and A3represents N, A4represents N, A5represents CR7and A6represents CR7; or n denotes 1 and A3represents N, A4represents CR7, A5represents N and A6represents CR7; or n denotes 1 and A3represents N, A4represents CR7, A5represents CR7and A6represents N; or n denotes 1 and A3represents CR7, A4represents N, A5represents CR7and A6represents N; or n denotes 1 and A3represents CR7, A4represents N, A5represents N and A6represents CR7; or n denotes 1 and A3represents CR7, A4represents CR7, A5represents N and A6represents N; or n denotes 0 and A3represents S, A4represents CR7and A5represents CR7; or n denotes 0 and A3represents S, A4represents CR7and A5represents N; or n denotes 0 and A3represents O, A4represents CR7and A5represents CR7, or n denotes 0 and A3represents O, A4represents CR7and A5represents N; or n denotes 0 and A3represents CR7, A4represents CR7and A5represents S; or n denotes 0 and A3represents N, A4represents CR7and A5represents S; orn denotes 0 and A3represents CR7, A4represents CR7and A5represents O; or n denotes 0 and A3represents N, A4represents CR7and A5represents O.

[0306] In further embodiments, R1represents the partial structure:wherein: R14aand R14beach independently of the other represent H; F; Cl; Br; CF3; CN; OH; OCF3; NH2; C1-4-aliphatic residue, O—C1-4-aliphatic residue, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, I, O—C1-4-aliphatic residue, OH and OCF3; or independently represent C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case saturated or unsaturated, unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, C1-4-aliphatic residue, OH, ═O, O—C1-4- aliphatic residue, OCF3, NH2, NH(C1-4-aliphatic residue) and N(C1-4-aliphatic residue)2; m represents 0, 1, 2 or 3; Y represents O or NR15, wherein R15represents H or C1-4-aliphatic residue, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly- substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, C1-4-aliphatic residue, OH, O—C1-4-aliphatic residue, OCF3, NH2, NH(C1-4-aliphatic residue) and N(C1-4-aliphatic residue)2; or C3-10-cycloaliphatic residue, saturated or unsaturated, unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, C1-4-aliphatic residue, OH, O—C1-4-aliphatic residue, OCF3, NH2, NH(C1-4-aliphatic residue) and N(C1-4-aliphatic residue)2; o represents 0 or 1, B represents C1-8-aliphatic residue, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly- substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, CN, OH, ═O, O—C1-4-aliphatic residue, OCF3, C(═O)OH, CF3, NH2, NH(C1-4-aliphatic residue) and N(C1-4-aliphatic residue)2; or C3-10-cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case saturated orunsaturated, unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, CN, OH, O— C1-4-aliphatic residue, OCF3, C1-4-aliphatic residue, C(═O)—OH, CF3, NH2, NH(C1-4- aliphatic residue), N(C1-4-aliphatic residue)2and SCF3; or aryl or heteroaryl, in each case unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, NO2, CN, OH, O—C1-4- aliphatic residue, OCF3, C1-4-aliphatic residue, C(═O)OH, CF3, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, S—C1-4-aliphatic residue, SCF3, benzyl, phenyl, pyridyl and thienyl, wherein benzyl, phenyl, pyridyl, thienyl can in each case be unsubstituted or mono- or poly-substituted by one or more substituents selected independently of one another from the group consisting of F, Cl, Br, NO2, CN, OH, O—C1-4-aliphatic residue, OCF3, C1-4- aliphatic residue, C(═O)—OH, CF3, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, S—C1-4-aliphatic residue and SCF3.

[0307] In further embodiments, R14aand R14beach independently of the other represents H; F; Cl; CH3; CH2CH3; (CH2)2CH3; CH(CH3)2; (CH2)3CH3; CH(CH)3CH2CH3; C(CH3)3; OH; OCH3; OCH2CH3; O(CH2)2OCH3or O(CH2)2OH; m represents 0, 1 or 2 and represents 0 and B represents CH3; CH2CH3; (CH2)2CH3; CH(CH3)2; (CH2)3CH3; CH(CH3)CH2CH3; C(CH3)3; cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; cycloheptyl; adamantyl; bicyclo[2.2.1]heptyl; bicyclo[2.2.2]octyl; phenyl, pyridyl or thienyl, in each case unsubstituted or mono-, di- or tri-substituted by one, two or three substituents each selected independently of one another from the group consisting of F, Cl, CN, OH, O—C1-4-aliphatic residue, OCF3, C1-4-aliphatic residue, CF3, NH2, NH(C1-4-aliphatic residue) and N(C1-4- aliphatic residue)2.

[0308] In further embodiments, R2; R3; R4; R5; R10, R11, R12and R13each independently of the others represents H; F; Cl; CF3; CN; OH; OCF3; SCF3; CH3; CH2CH3; (CH2)2CH3; CH(CH3)2; (CH2)3CH3; CH(CH)3CH2CH3; C(CH3)3; OCH3; OCH2CH3; O(CH2)2OCH3; O(CH2)2OH; SCH3; SCH2CH3; cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; or R2and R3or R4and R5or R10and R11or R12and R13or R2and R11or R2and R4or R2and R13or R4and R13or R4and R11or R12and R13, together with the carbon atom(s) joining them, form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in each case unsubstituted; wherein the remaining substituents R2, R3; R4; R5; R10, R11, R12and R13in each case have the meaning given above.

[0309] In further embodiments, each R7represents H, F; Cl; CN; CF3; CHF2; CH2F; OCF3; OCHF2; OCH2F; SCF3; CH3; CH2CH3; CH2CH2CH3; CH(CH3)2; OH2CH2CH2CH3;CH(CH)3CH2CH3; CH2CH(CH3)2; O(CH3)3; OCH3; OCH2CH3; O(CH2)2OCH3; O(CH2)2OH; S(═O)2CH3S(═O)2CH2CH3S(═O)2CH(CH3)2or S(═O)2CH2CH2CH3; and R8represents H or CH3or CH2CH3or CH(CH3)2.

[0310] In further embodiments, R6represents a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case saturated or unsaturated, unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, I, NO2, CN, OH, ═O, O—C1-4-aliphatic residue, OCF3, C1-4-aliphatic residue, CF3, SH, S—C1-4-aliphatic residue and SCF3; or an aryl or a heteroaryl, in each case unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, I, NO2, CN, OH, O—C1-4-aliphatic residue, OCF3, C1-4-aliphatic residue, CF3, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, SH, S—C1-4-aliphatic residue and SCF3.

[0311] In further embodiments, R6represents phenyl, pyridyl or thienyl, in each case unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, CN, OH, O—C1-4- aliphatic residue, OCF3, C1-4-aliphatic residue, CF3and SCF3.

[0312] In further embodiments, A1represents S; and A2represents S, S(═O)2or CR12R13, wherein R12and R13both represent H or both represent F; and R1represents the partial structure:wherein: R14aand R14beach independently of the other represents H; F; Cl; CH3; CH2CH3; (CH2)2CH3; CH(CH3)2; (OH2)3CH3; CH(CH)3CH2CH3; C(CH3)3; OH; OCH3; OCH2CH3; O(CH2)2OCH3; or O(CH2)2OH; m represents 0, 1 or 2 and B represents phenyl or naphthyl or pyridyl or thienyl, in each case unsubstituted or mono- or di- or tri-substituted by one, two or three substituents each selected independently of one another from the group consisting of F, Cl, CN, OH, O-1-4-aliphatic residue, OCF3, C1-4-aliphatic residue, C(═O)—OH, CF3, NH2, NH(C1-4-aliphatic residue) and N(C1-4-aliphatic residue)2; R2, R3, R4; R5, R10, R11, R12and R13each independently of the others represent H; F; Cl; Br; I; NO2; CF3; CN; OH; OCF3; SH; SCF3; CH3; CH2CH3; CH2CH2CH3; CH(CH3)2; CH2CH2CH2CH3; CH(CH)3CH2CH3; CH2CH(CH3)2; C(CH3)3; OCH3; OCH2CH3; O(CH2)2OCH3; O(CH2)2OH; SCH3; SCH2CH3; cyclopropyl; cyclobutyl; cyclopentyl; cyclohexyl; or R2and R3or R4and R5or R10and R11or R12and R13or R2and R11or R2and R4or R2and R13or R4and R13or R4and R11or R12and R13, together with the carbon atom(s) joining them, form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in each case unsubstituted; wherein the remaining substituents R2, R3; R4; R5; R10, R11, R12and R13in each case have the meaning given above; R6represents phenyl, in each case unsubstituted or mono- or poly-substituted by one or more substituents each selected independently of one another from the group consisting of F, Cl, Br, I, CN, OH, OCH3, OCH2CH3, OCF3, CH3, CH2CH3, CH(CH3)2and CF3; each R7represents H, F; CI; CN; CF3; CHF2; CH2F; OCF3; OCHF2; OCH2F; SCF3; CH3; CH2CH3; CH2CH2CH3; CH(CH3)2; CH2CH2CH2CH3; CH(CH)3CH2CH3; CH2CH(CH3)2; C(CH3)3; OCH3; OCH2CH3; O(CH2)2OCH3; O(CH2)2OH; S(═O)2CH3S(═O)2CH2CH3, S(═O)2CH(CH3)2or S(═O)2CH2CH2CH3; and R8represents H or CH3or CH2CH3or CH(CH3)2.

[0313] In further embodiments, the Kv7 channel activator is selected from the group consisting of: 12-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-(3-methyl-butyl)- benzamide; 2 N-(3,3-Dimethyl-butyl)-2-[3-(4-fluorophenyl)-propylsulfanyl]-benzamide; 33- [[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-(3-methyl-butyl)-pyridine-2-carboxylic acid amide; 43-[2-(Benzenesulfonyl)-ethylsulfanyl]-N-(thiophen-2-yl-methyl)-pyridine-2- carboxylic acid amide; 54-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-(3-methyl- butyl)-pyridine-3-carboxylic acid amide; 64-[[3,3-Difluoro-3-(4-fluorophenyl)- propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-pyridine-3-carboxylic acid amide; 73-[[3,3- Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-(3-methyl-butyl)-pyridine-4-carboxylic acid amide; 83-[2-(Benzenesulfonyl)-ethylsulfanyl]-N-(thiophen-2-yl-methyl)-pyridine-4- carboxylic acid amide; 93-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-(3-methyl- butyl)-pyrazine-2-carboxylic acid amide; 104-[[3,3-Difluoro-3-(4-fluorophenyl)- propyl]sulfanyl]-N-(3-methyl-butyl)-pyrimidine-5-carboxylic acid amide; 114-[[3,3- Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-pyrimidine-5- carboxylic acid amide; 123-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-(3-methyl- butyl)-pyridazine-4-carboxylic acid amide; 133-[[3,3-Difluoro-3-(4-fluorophenyl)- propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-pyridazine-4-carboxylic acid amide; 144- [[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-thiazole-5- carboxylic acid amide; 154-[[3,3-Difluoro-3-(4-fluorophenyl)-propyl]sulfanyl]-N-[(4-fluorophenyl)-methyl]-2-methyl-thiazole-5-carboxylic acid amide; in the form of a free compound, a solvate and / or a physiologically acceptable salt. Formula 21

[0314] In another embodiment, the Kv7 channel activator may be selected from one of the following compounds. Such compounds are described in US Publication No. US20140148454A1, published May 29, 2014 and corresponding to US Application No. 14 / 091,378 filed November 27, 2013; International Publication No. WO2014082739A1, published June 5, 2014 and corresponding to International Application No. PCT / EP2013 / 003574 filed November 27, 2013; which are incorporated by reference in their entirety herein. In the case of any conflict of terminology in the context of Formula 21, these references incorporated by reference herein control.

[0315] In an embodiment, the Kv7 channel activator is a compound according to formula 21: Formula 21wherein, A1represents CR5or N; A2represents CR6, N, O, S or NR7; A3represents CR8or N, and n denotes 0 or 1, on the condition, that if n denotes 0, then A2represents O, S or NR7, or if n denotes 1, then A2represents CR6or N, wherein R5is selected from F, Cl, Br, CN, CH3, CF3, CHF2, CH2F, OCH3, C2H5, SCH3, OCF3, OCHF2or OCH2F; R6is selected from H, F, Cl, Br, CN, CH3, CF3, CHF2, CH2F, OCH3, C2H5, SCH3, OCF3, OCHF2or OCH2F; R7represents C1-4-aliphatic residue or C3-5-cycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted; R8is selected from H, F, Cl, Br, CN, CH3, CF3, CHF2, CH2F, OCH3, C2H5, SCH3, OCF3, OCHF2or OCH2F; with the proviso, that, if n denotes 1, then at least one of A1, A2and A3denotes N, with the proviso, that if n denotes 1 and A3denotes N, then A1and / or A2denotes N, and with the proviso, that if n denotes 1 and A2denotes N and A1denotes CR5and A3denotes CR8, then R5denotes F, Cl, CH3, CF3, CHF2or CH2F; R13represents H or C1-4-aliphatic residue, R1represents C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; or C3-10-cycloaliphatic residue or 3 to 10 memberedheterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; or aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; R2represents a C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted; a C3-6-cycloaliphatic residue or a 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted, or denotes S—R9, O—R10or N(R11R12), wherein R9and R10in each case represent C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-6-cycloaliphatic residue or 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; with the proviso, that if R9or R10denote a 3 to 7 membered heterocycloaliphatic residue, than the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom, R11represents C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted; C3-6-cycloaliphatic residue or a 3 to 7 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; with the proviso that if R11denotes a 3 to 7 membered heterocycloaliphatic residue, the 3 to 7 membered heterocycloaliphatic residue is linked via a carbon atom; and R12denotes C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted; or R11and R12form together with the nitrogen atom connecting them a 3 to 7 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted; R3represents C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; or C3-10- cycloaliphatic residue or 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4- aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; or aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted and in each case optionally linked via a C1-4-aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted; on the condition that if R3denotes a 3 to 10 membered heterocycloaliphatic residue or a heteroaryl, the 3 to 10 membered heterocycloaliphatic residue or the heteroaryl is linked via a carbon atom; and R4denotes H or C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted; or R3and R4form together with the nitrogen atom connecting them a 3 to 10 membered heterocycloaliphatic residue, unsubstituted or mono- or polysubstituted; in which an “aliphatic group” and “aliphatic residue” may in each case be branched orunbranched, saturated or unsaturated, in which a “cycloaliphatic residue” and a “heterocycloaliphatic residue” may in each case be saturated or unsaturated, in which “mono- or polysubstituted” with respect to an “aliphatic group”, an “aliphatic residue”, a “cycloaliphatic residue” and a “heterocycloaliphatic residue” relates, with respect to the corresponding residues or groups, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, NH—C(═O)— C1-4-aliphatic residue, N(C1-4aliphatic residue)-C(═O)—C1-4aliphatic residue, NH— S(═O)2—C1-4aliphatic residue, N(C1-4aliphatic residue)-S(═O)2—C1-4aliphatic residue, ═O, OH, OCF3, O—C1-4-aliphatic residue, O—C(═O)—C1-4-aliphatic residue, SH, SCF3, S—C1-4-aliphatic residue, S(═O)2OH, S(═O)2—C1-4-aliphatic residue, S(═O)2—O—C1-4-aliphatic residue, S(═O)2—NH(C1-4-aliphatic residue), S(═O)2—N(C1-4-aliphatic residue)2, CN, CF3, CHO, COOH, C1-4-aliphatic residue, C(═O)—C1-4-aliphatic residue, C(═O)—O—C1-4- aliphatic residue, C3-6-cycloaliphatic residue, 3 to 7 membered heterocycloaliphatic residue, C(═O)NH2, a C(═O)—NH(C1-4-aliphatic residue) and C(═O)—N(C1-4-aliphatic residue)2; in which “mono- or polysubstituted” with respect to “aryl” and a “heteroaryl” relates, with respect to the corresponding residues, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2,NH(C1-4-aliphatic residue), N(C1-4-aliphatic residue)2, NH—C(═O)—C1-4-aliphatic residue, N(C1-4aliphatic residue)- ...

Claims

CLAIMS 1. A pharmaceutical composition comprising a metal channel activator and an NMDA receptor antagonist.

2. The pharmaceutical composition of Claim 1, wherein the metal channel activator is a potassium channel activator.

3. The pharmaceutical composition of 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 of Claim 3 or 4, wherein the Kv7 channel activator is a Kv7.2 / 7.3 channel activator.

6. The pharmaceutical composition of 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 of 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 of 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 of the disclosed compounds according to any one or more of formulas 1 to 171.

9. The pharmaceutical composition of any one of claims 1 to 8, wherein the metal channel activator is10. The pharmaceutical composition of any one of claims 1 to 8, wherein the metal channel activator is.

11. The pharmaceutical composition of any one of claims 1 to 10, wherein the NMDA receptor antagonist is ketamine, lanicemine, dextromethorphan (DXM), phencyclidine (PCP), methoxetamine (MXE), or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of any one of claims 1 to 11, wherein the NMDA receptor antagonist or a pharmaceutically acceptable salt thereof is in a form of a prodrug.

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

14. The pharmaceutical composition of Claim 13, wherein the lanicemine or a pharmaceutically acceptable salt thereof is in a form of a prodrug.

15. The pharmaceutical composition of Claim 14, wherein the prodrug of lanicemine has the following structure:

16. The pharmaceutical composition of Claim 14 or 15, wherein the prodrug of lanicemine has the following structure:

17. A method of treating a depressive disorder, comprising administering the pharmaceutical composition of any one of Claims 1-17.

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 the pharmaceutical composition of any one of Claims 1-16.

20. The method of Claim 19, wherein neurological or neurodegenerative disorder is amyotrophic lateral sclerosis, bipolar disorder, treatment resistant and major depression, general anxiety disorder, panic disorder, social anxiety, mood disorders, cognitive disorders, dementia, agitation, apathy, psychoses, post-traumatic stress disorders, irritability, disinhibition, learning disorders, memory loss, personality disorders, bipolar disorders, Rett syndrome, eating disorders, conduct disorder, 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 the pharmaceutical composition of any one of Claims 1-16.

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 afflicted with a disorders in which a metal channel activator is clinically relevant, said kit including: (a) the metal channel activator; and (b) instructions for administering said metal channel activator in combination with an NMDA receptor antagonist by one of the methods of Claims 17-23.

25. A kit for treating a patient afflicted with a disorder in which an NMDA receptor antagonist is clinically relevant, said kit including: (a) the NMDA receptor antagonist; and (b) instructions for administering said NMDA receptor antagonist with a metal channel activator by one of the methods of Claims 17-23.

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