Combination therapy including a metal channel activator and an NMDA receptor antagonist

Abstract

Pharmaceutical compositions containing a metal channel activator and an NMDA receptor antagonist are provided. Also provided are methods for treating depressive disorders, comprising administering the pharmaceutical compositions. Also provided are methods for treating neurological or neurodegenerative disorders, comprising administering the pharmaceutical compositions. Also provided are methods for treating pain disorders, comprising administering the pharmaceutical compositions.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This international patent application claims priority to U.S. Provisional Patent Application No. 63 / 402,416, filed August 30, 2022, which is incorporated herein by reference in its entirety.

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

[0003] Metal channel activators (openers) are involved in a wide range of physiological functions, including the regulation of the electrical properties of excitable cells. Metal channels allow potassium (K) transport across the cell membrane. + ) and sodium (Na + The main function of these channels in the brain is to regulate neuronal action potentials. Several neurological disorders potentially result from dysregulation of metal channels.

[0004] Potassium (K) is present on the plasma membrane of most cell types. + ) channels are the most diverse class of all ion channels. + The Kv7 family of voltage-gated potassium (K) channels is of particular therapeutic interest due to their importance in neurological conditions such as excitatory disorders, including amyotrophic lateral sclerosis (ALS). + ) There are five members of the Kv7 family of channels.

[0005] Metal channel activators have been reported to be useful in treating various neurological and neurodegenerative disorders. To date, only one metal channel activator, retigabine, has been FDA-approved. Retigabine is used as an anticonvulsant for the treatment of epilepsy. Additional 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 Kv7 Channels as a New Therapeutic Tool for Multiple Brain Disorders. Front Physiol. 2020 Jun 19;11:688. doi:10.3389 / fphys.2020.00688). However, there remains a need for new therapies that utilize Kv7. One solution is to combine metal channel activators with other therapeutic agents to significantly improve treatment outcomes.

[0006] NDMA receptor antagonists target the NDMA receptor, a receptor that allows calcium efflux in the presence of glutamate or glycine when neurons are depolarized. NDMA receptor antagonists prevent calcium efflux and are used as anesthetics. Recent studies, primarily focusing on ketamine, have revealed unexpected antidepressant effects. Lanisemine has been developed as an alternative antidepressant to ketamine with reduced side effects, but has not been successful in treating depression as a single agent in randomized controlled trials.

[0007] Described herein are compositions and methods for combination therapy of Kv7 openers with NMDA receptor antagonists. Combination therapy has superior therapeutic potential compared to either Kv7 openers or NMDA receptor antagonists alone and may be particularly useful for treating depressive disorders. Pharmaceutical compositions combining these agents may also be useful for treating pain and neurological or neurodegenerative disorders. These two agents target distinct molecular targets associated with depressive disorders, pain disorders, neurological disorders, and neurodegenerative disorders. Specifically, Kv7 channel openers reduce excitability, while NMDA receptor antagonists reduce the efflux of cations such as calcium. The inventors have discovered that combining a Kv7 opener and an NMDA receptor antagonist, as described herein, results in improved therapeutic outcomes. Summary of the Invention

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

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

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

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

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

[0013] The following detailed description is provided to assist those skilled in the art in practicing the present invention. Exemplary embodiments are described in detail hereinafter. However, these embodiments are merely exemplary, and the present disclosure is not limited thereto, but rather is defined by the scope of the appended claims. Those skilled 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, embodiments are described below merely by reference to structures and schemes to illustrate aspects of the specification. 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." When preceding a list of elements, phrases such as "at least one of" modify the entire list of elements, and not each individual element of the list.

[0015] Terms such as first, second, and third may be used herein to describe various elements, components, regions, layers, and / or sections, but it should be understood that these elements, components, regions, layers, and / or sections are not limited by these terms. These terms are used only 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 referred to as a second element, component, region, layer, or section without departing from the teachings of embodiments of the present invention.

[0016] As used herein, the terms "comprises" and / or "comprising" or "includes" and / or "including" specify the presence of stated features, regions, integers, steps, operations, elements, and / or components, but are to be understood as not excluding 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 those skilled in the art to which this disclosure belongs. The terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting. Terms, such as those defined in commonly used dictionaries, should be interpreted to have a meaning consistent with their meaning in the relevant technical field and in the context of this disclosure, and should not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0018] As used herein, except as expressly provided herein, each of the following terms shall have the meaning set forth below. Additional definitions are set forth throughout this application. If a term is not specifically defined herein, the term will be given the art-recognized meaning by those of ordinary skill in the art who apply the term in the context of 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, unless a specific definition is provided otherwise, the term "substituted" refers to a group in which at least one hydrogen atom of a substituent or compound is substituted with a cyano group (-CN), a hydroxy group (-OH), an amino group (-NH), a carboxyl group (-COH), a substituted or unsubstituted C1-C10 amine group, a nitro group (-NO), a C1-C10 alkyl group, a C3-C10 cycloalkyl group, a C6-C12 aryl group, a C1-C10 alkoxy group, a C1-C10 trifluoroalkyl group such as a trifluoromethyl group (-CF3), or a cyano group (-CN) in place of at least one hydrogen atom of a substituent or compound.

[0021] Additional aspects will be described in part and will be apparent in part from the description that follows.

[0022] As used herein, the terms "modulator," "modulators," and "modulating," when describing a compound, describe compounds that may produce their effects through several mechanisms of action, including, but not limited to, binding to the active site of a protein, binding to a region of a protein away from the active site, causing protein relocalization, inducing protein degradation, inducing protein stabilization, causing a conformational change in a protein, decreasing the activation threshold of a protein, increasing the activation threshold of a protein, altering post-translational modifications of a protein, reducing gene transcription, increasing gene transcription, decreasing translation of an mRNA transcript, increasing translation of an mRNA transcript, disrupting an interaction between two proteins, and stabilizing an interaction between two proteins, where the protein may be the target of modulation or an intermediate protein involved in the modulation of the target protein. Modulators of the targets (i.e., Kv7 and NMDA receptor) described herein, respectively, or both, may be small molecule compounds, proteins, antibody fragments or antibodies, or any other constructs that effect modulation. It should be understood that an NMDA receptor antagonist is a type of NMDA receptor modulator.

[0023] As used herein, "NMDA receptor antagonist" or alternatively "NMDA modulator" refers to any compound (small molecule, peptide, etc.) that modulates or produces a desired change in the biological activity of an NMDA receptor. In various embodiments, an NMDA receptor antagonist may target a specific portion of the NMDA receptor, such as the GluN1 (alternatively, NR1) or GluN2 (alternatively, NR2) subunit, or additionally or alternatively the GluN3 subunit. In embodiments, an NMDA receptor antagonist targets, optionally selectively, the GluN1 subunit. In embodiments, an NMDA receptor antagonist targets, optionally selectively, one or more GluN2 subtypes GluN2A, GluN2B, GluN2C, and / or GluN2D. In some embodiments, an NMDA receptor antagonist may target, optionally selectively, one or more GluN3 subtypes GluN3A, GluN3B, and / or GluN3C. In some embodiments, an NMDA receptor antagonist may target an allosteric site. In some embodiments, NMDA receptor antagonists may include partial agonists, which exert a dual (agonist / antagonist) effect on the NMDA receptor. In certain embodiments, NMDA receptor antagonists may include agents with targets other than the NMDA receptor that produce NMDA receptor antagonist-like physiological effects.

[0024] As used herein, "neurological disease" refers to a disease or disorder that affects nerves found in the brain and / or elsewhere in the body. Such neurological diseases may include: defects of the septum pellucidum, acid lipase disease, acute disseminated encephalomyelitis, adrenoleukodystrophy, agenesis of the corpus callosum, agnosia, Aicardi syndrome, Aicardi-Goutières 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 malformations, Asperger's syndrome, ataxia-telangiectasia, ataxia, 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 idiopathic blepharospasm, Binswanger's disease, brachial plexus injuries, brain and spinal cord tumors, Brown-Séquard syndrome, CADASIL, Canavan disease, carpal tunnel syndrome, central spinal cord syndrome, central pain syndrome, central pontine myelinolysis, head injuries, cerebellar degeneration, cerebellar hypoplasia, cerebral aneurysms, cerebral arteriosclerosis, cerebral atrophy, cerebral cavernous malformations, cerebral hypoxia, cerebral palsy, cerebro-oculofacial-skeletal syndrome (COFS), Charcot -Marie-Tooth disease, Chiari malformation, chorea, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic pain, Coffin-Lowry syndrome, posterior horn enlargement of the lateral ventricles, 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 coordination disorder, diabetic neuropathy, Dravet syndrome, autonomic neuropathy, dysgraphia, dyslexia, myofascial instability Clonus cerebellar dyssynergia, dystonia, empty sella syndrome, encephalitis lethargica, encephalocele, encephalopathy, epilepsy, Erb-Duchenne and Degerines-Krampke palsy, essential tremor, Fabry disease, Fahr syndrome, familial periodic paralysis, Farber disease, febrile seizures, fibromuscular dysplasia, foot drop, Friedreich's ataxia, frontotemporal dementia, functional neurological disorders, Gaucher disease, systemic gangliosidosis, Gerstmann syndrome, Gerstmann-Straussler-Scheinker disease, giant axonal neuropathy, glossopharyngeal neuralgia,Guillain-Barré syndrome, headache, persistent hemicrania, hemifacial spasm, hereditary neurological disorders, 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's disease, infantile spasms, inflammatory myopathy, occipital forencephalon prolapse, Isaacs syndrome, Joubert syndrome, Kearns-Sayre syndrome, Kennedy disease, Kleine-Levin syndrome, Klippel-Feil syndrome, Klippel-Trenaunay syndrome (KT) S), Klüver-Bucy syndrome, Krabbe disease, kuru, Lambert-Eaton myasthenic syndrome, Landau-Kleffner syndrome, learning disabilities, Leigh's disease, Lennox-Gastaut syndrome, Lesch-Nyhan syndrome, cerebral leukodystrophy, lipid storage diseases, lipoid proteinosis, lissencephaly, locked-in syndrome, Machado-Joseph disease and spinocerebellar ataxia, megaloencephaly, Merkelson-Rosenthal syndrome, meningitis and encephalitis, Menkes disease, dysesthesias femoral neuralgia, metachromatic leukodystrophy, microcephaly, migraine, Miller-Fisher syndrome, mitochondrial myelopathy Opathies, Moebius syndrome, single limb muscular atrophy, motor neuron disease, moyamoya disease, mucolipidosis, mucopolysaccharidosis, multi-infarct dementia, multifocal motor neuropathy, multiple sclerosis, multiple system atrophy, multiple system atrophy with orthostatic hypotension, muscular dystrophy, myasthenia gravis, myoclonus, myotonia, myotonia congenita, narcolepsy, neuroacanthocytosis, neurodegeneration with cerebral 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 disorder, 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 migraine, Parry-Romberg syndrome, Pelizaeus-Merzbacher disease, peripheral neuropathy, periventricular leukomalacia, pervasive developmental disorder, radiculopathy, piriformis syndrome, pituitary tumor, polymyositis, Pompe disease, porencephaly, post-polio syndrome, postural orthostatic tachycardia syndrome,Primary lateral sclerosis, progressive multifocal leukoencephalopathy, progressive supranuclear palsy, prosopagnosia, pseudotumor cerebri, Rasmussen's encephalitis, Refsum's disease, repetitive movement disorder, restless legs syndrome, Rett's syndrome, Reye's syndrome, Sandhoff's disease, Schilder's disease, schizencephaly, septo-optic dysplasia, shaken baby syndrome, shingles, Sjogren's syndrome, sleep apnea, Sotos syndrome, convulsions, spina bifida, spinal cord infarction, spinal cord injury, spinal muscular atrophy, stiff-person syndrome, striatonigral degeneration, stroke, Sturgey-Weber syndrome, subacute sclerosing panencephalitis, SUNCT headache, dysphagia, Sydenham's chorea, ataxia Diagnosis: Diagnosis, syringomyelia, tabes dorsalis, tardive dyskinesia, Tarlov cyst, Tay-Sachs disease, tethered spinal cord syndrome, thoracic outlet syndrome, thyrotoxic myopathy, Todd's palsy, Tourette's syndrome, transient ischemic attack, transmissible spongiform encephalopathy, transverse myelitis, traumatic brain injury, tremor, trigeminal neuralgia, tropical spastic paraparesis, Treuer's syndrome, tuberous sclerosis, vasculitis syndromes of the central and peripheral nervous system, von Hippel-Lindau disease (VHL), Wallenberg syndrome, Wernicke-Korsakoff syndrome, whiplash, Whipple's disease, Williams syndrome, Wilson's disease, and Zellweger syndrome.

[0025] As used herein, the term "metal channel activator" is intended to include both metal channel activators and pharmaceutically acceptable salts thereof.

[0026] As used herein, the term "NMDA receptor antagonist" or "NMDA modulator" is intended to include both NMDA receptor antagonists and pharmaceutically acceptable salts thereof.

[0027] As used herein, the term "AUC" refers to the definite integral of the concentration of a drug in blood, cerebrospinal fluid, a target organ, or any other physiologically relevant site after a dose is administered as a function of time. In this context, AUC is used to measure the total exposure to a drug over time. AUC can be assessed over a fixed time interval or estimated based on the integrated drug concentration measured over a time interval extrapolated to infinite time.

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

[0029] As used herein, the term "Tmax" is the time after administration required for a drug to reach its maximum 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 "proteinopathy" refers to a disease characterized by the accumulation or aggregation of a protein or proteins, including, but not limited to, Creutzfeldt-Jakob disease and other prion diseases, Alzheimer's disease, Parkinson's disease, amyloidosis, multiple system atrophy, amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration, and dementia with Lewy bodies.

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

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

[0033] Metal channel activators Examples of metal channel activators, including Kv7 channel activators, are disclosed in Formulas 1-171, the section entitled "Further Embodiments," and in the corresponding referenced applications.

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

[0035] In embodiments, the Kv7 channel activator is a compound according to Formula 1: [ka] wherein D is an optionally substituted C 3~6 Carbocyclyl, optionally substituted C 2~5 heterocyclyl, isopropyl, or t-butyl; Bz is optionally substituted benzimidazol-1,2-diyl; A is C 1~8 alkyl, X is F, and Y is H, F, Cl, Br, I, or a moiety having a molecular weight of 15 Da to 300 Da and consisting of 2 to 5 chemical elements, the chemical elements being 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, and 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, which 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 an optionally substituted C 3~6 Carbocyclyl, optionally substituted C 2~5 heterocyclyl, isopropyl, or t-butyl; Bz is optionally substituted benzimidazol-1,2-diyl; A is C 1~8 alkyl, 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, the chemical elements being 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 a further embodiment, each of the D, X, and Y substituents, if present, independently has a molecular weight of 15 Da to 200 Da and consists of 2 to 5 chemical elements, which chemical elements are independently C, H, O, N, S, F, Cl, or Br.

[0041] In a further embodiment, R 1 is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 It is a hydroxyalkyl.

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

[0043] In a further embodiment, X is CF3.

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

[0045] In a further embodiment, X is H.

[0046] In a further embodiment, Y is H.

[0047] In a further embodiment, Y is OH.

[0048] In a further embodiment, the Kv7 channel activator is a compound selected from the group consisting of: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

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

[0050] In embodiments, the Kv7 channel activator is a compound according to Formula 2: [ka] wherein D is optionally substituted cyclobutyl, optionally substituted phenyl, optionally substituted isoxazolyl, optionally substituted pyridinyl, isopropyl, or t-butyl; and A is C 2~8alkyl; X is H, F, CF3, optionally 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, the chemical elements being independently C, H, O, N, S, F, Cl, or Br; and R 1 are F, Cl, Br, CN, OCH3, CHF2, CF3, C 1~4- CO2-Alkyl, C 1~4 alkyl, -CH2CO2H, -CH2CO2CH2CH3, or -CH2CON(CH3)2, or C 1~5 hydroxyalkyl, and R 2 , R 3 , and R 4 are 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, CF, OH, C 1~5 O-Alkyl, C 0~6 alkylamino, optionally substituted tetrahydropyranyl, or C 0~6 It is a fluoroalkylamino.

[0052] In a further embodiment, R 1 is Cl, Br, -OCH3, -CN, -CF3, -CH2OH, -COOCH2CH3, -C(CH3)2OH, -CHOHCH2CH3, -CHOHCH3, -CHF2, -CH(CH3)2, -C(CH2CH3)2OH, -CH2COOCH2CH3, -CH2C(CH3)2OH, -CH2COOH, or -CH2CON(CH3)2.

[0053] In a further embodiment, R 2 is H, F, —CH2OH, —CO2Me, or —C(CH3)2OH.

[0054] In a further embodiment, R 3 is H.

[0055] In a further embodiment, R 4 is H, —CH3, or —CF3.

[0056] In a further embodiment, R 1 is Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 It is a hydroxyalkyl.

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

[0058] In a further embodiment, X is CF3.

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

[0060] In a further embodiment, X is H.

[0061] In a further embodiment, Y is H.

[0062] In a further embodiment, Y is OH.

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

[0064] In a further embodiment, the Kv7 channel activator is a compound according to formula 2, wherein D is optionally substituted cyclobutyl or t-butyl, and A is C 2~8 alkyl, X is H, CF3, or optionally substituted phenyl, Y is H or OH, and R 1 is CN or C 1~4 hydroxyalkyl, and R 2 , R 3 , and R 4 are independently H or F.

[0065] In a further embodiment, R 1 is CN, —C(CH3)2OH, or —CH2C(CH3)2OH.

[0066] In a further embodiment, R 2 is F.

[0067] In a further embodiment, R 3 is H.

[0068] In a further embodiment, R 4 is H.

[0069] In a further embodiment, R 1 is CN.

[0070] In a further embodiment, R 1 is C 1~4 It is a hydroxyalkyl.

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

[0072] In a further embodiment, X is CF3.

[0073] In a further embodiment, X is H.

[0074] In a further embodiment, Y is H.

[0075] In a further embodiment, Y is OH.

[0076] In a further embodiment, the Kv7 channel activator is a compound according to formula 2, wherein D is cyclobutyl and A is C 1~8 alkyl, X is CF3, Y is H, and R 1 , H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is 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, the chemical elements being independently C, H, O, N, S, F, Cl, or Br; R 4 is H, -CH3, or -CF3, or D is optionally substituted cyclobutyl and A is C 1~8 alkyl, X is CF3, Y is H, and R 1 , H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is H and R 4 is H, -CH3, or -CF3, or D is t-butyl and A is C1~8 alkyl, X is H, Y is H, and R 1 But, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is 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, the chemical elements being independently C, H, O, N, S, F, Cl, or Br; R 4 is H, -CH3, or -CF3, or D is t-butyl and A is C 1~8 alkyl, X is CF3, Y is H, and R 1 , H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is 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, the chemical elements being independently C, H, O, N, S, F, Cl, or Br; R 4 is H, -CH3, or -CF3, or D is cyclobutyl and A is C 1~8 alkyl, X is H, Y is methyl(2,2,2-trifluoroethyl)amino, and R 1 , H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is H and R 4is H, -CH3, or -CF3, or D is cyclobutyl and A is C 1~8 alkyl, X is CF3, Y is dimethylamino, and R 1 , H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is H and R 4 is H, -CH3, or -CF3, or D is optionally substituted cyclobutyl, optionally substituted phenyl, or optionally substituted C 2~5 A is alkyl, the optional substituents are selected from -CH and F, A is C alkyl, X is substituted cyclobutyl, the substituents are F, Y is H, and R 1 is selected from H, C3 hydroxyalkyl, CN, F, or Cl, and R 2 is selected from H, CN, F, Br, or -OCF3, and R 3 is selected from H, F, or -OCH3, and R 4 is H or F, and when X is substituted with two fluorine atoms, the fluorine atoms are not geminal, or a pharmaceutically acceptable salt thereof.

[0077] In embodiments, the Kv7 channel activator is a compound according to Formula 2, wherein R 1 , R 2 , R 3 , and R 4 are 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, CF, OH, C1~5 O-Alkyl, C 0~6 alkylamino, optionally substituted tetrahydropyranyl, or C 0~6 It is a fluoroalkylamino.

[0079] In a further embodiment, R 1 is H, Cl, Br, -OCH3, -CN, -CF3, -CH2OH, -COOCH2CH3, -C(CH3)2OH, -CHOHCH2CH3, -CHOHCH3, -CHF2, -CH(CH3)2, -C(CH2CH3)OH, -CH2COOCH2CH3, -CH2C(CH3)2OH, -CH2COOH, or -CH2CON(CH3)2.

[0080] In a further embodiment, R 2 is H, F, —CH2OH, —CO2Me, or —C(CH3)2OH.

[0081] In a further embodiment, R 3 is H.

[0082] In a further embodiment, R 4 is H, —CH3, or —CF3.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

[0112] In an embodiment of Formula 2, D is optionally substituted cyclobutyl or t-butyl, and A is C2~8 alkyl, X is H, CF3, or optionally substituted phenyl, Y is H or OH, and R 1 CN or C 1~4 hydroxyalkyl, and R 2 , R 3 , and R 4 is independently H or F. In a further embodiment, R 1 is CN, —C(CH)OH, or —CHC(CH)OH. In a further embodiment, R 2 is F. In a further embodiment, R 3 is H. In a further embodiment, R 4 is H. In a further embodiment, R 1 is CN. In a further embodiment, R 1 is C 1~4 In a further embodiment, X is hydroxyalkyl. In a further embodiment, X is optionally substituted 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 and A is C 1~8 alkyl, X is CF3, Y is H, and R 1 is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is 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, the chemical elements being independently C, H, O, N, S, F, Cl, or B; R 4 is H, —CH3, or —CF3.

[0114] In an embodiment of Formula 2, D is optionally substituted cyclobutyl and A is C 1~8alkyl, X is CH, Y is H, and R 1 is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is H and R 4 is H, —CH3, or —CF3.

[0115] In an embodiment of Formula 2, D is t-butyl and A is C 1~8 alkyl, X is H, Y is H, and R 1 is Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is 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, the chemical elements being independently C, H, O, N, S, F, Cl, or Br; R 4 is H, —CH3, or —CF3.

[0116] In an embodiment of Formula 2, D is t-butyl and A is C 1~8 alkyl, X is CF3, Y is H, and R 1 is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -C(CH)OH, and R 3 is 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, the chemical elements being independently C, H, O, N, S, F, Cl, or Br; R 4 is H, CH3, or CF3.

[0117] In an embodiment of Formula 2, D is cyclobutyl and A is C 1~8 alkyl, X is H, Y is methyl(2,2,2-trifluoroethyl)amino, and R 1 is H, Cl, Br, CN, OCH3, CF3, -CO2CH2CH3, C 1~4 Alkyl, or C 1~4 hydroxyalkyl, and R 2 is H, F, -CHOH, -COMe, or -CH(CH)OH, and R 3 is H and R 4 is H, —CH3, or —CF3.

[0118] In an embodiment of Formula 2, D is optionally substituted cyclobutyl, optionally substituted phenyl, or optionally substituted C 2~5 A is alkyl, the optional substituents are selected from —CH and F, A is C alkyl, X is substituted cyclobutyl, the substituents are F, Y is H, and R 1 is selected from H, C3 hydroxyalkyl, CN, F, or Cl, and R 2 is selected from H, CN, F, Br, or -OCF3, and R 3 is selected from H, F, or —OCH3, and R 4 is H or F, and when X is substituted with two fluorine atoms, the fluorine atoms are not geminal, or a pharmaceutically acceptable salt thereof.

[0119] formula 3 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 3. Such compounds are described in U.S. Patent No. 8,293,911, issued October 23, 2012, and corresponding to U.S. Application No. 11 / 894,877, filed August 22, 2007, which is incorporated herein by reference in its entirety. In the event of any discrepancy in terminology relating to Formula 3, this reference, incorporated herein by reference, will control.

[0120] In embodiments, the Kv7 channel activator is a compound according to Formula 3: [ka] wherein R1 and R2 are independently variable and are selected from the group consisting of H, CN, halogen, CH2CN, OH, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(=O)C1-C6 alkyl, NH-C1-C6 alkyl, N(C1-C6 alkyl)-C1-C6 alkyl, NHC(=O)C1-C6 alkyl, C(=O)N(CH3)2, C(=O)N(Et)2, C(=O)NH2, C(=O)NH-C1-C6 alkyl, and SO2NH 2、 NHSO 2- C1-C6 alkyl, C(=O)OC1-C6 alkyl, OC(=O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2) m C3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2) m C3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CH2) m Thienyl, (CH2) m Imidazolyl, (CH2) m Pyrazyl, (CH2) m Oxazolyl, (CH2) m Isoxazolyl, (CH2) m Thiazolyl, (CH2) m Isothiazolyl, (CH2) m Phenyl, (CH2) m Pyrrolyl, (CH2) m Pyridyl, and (CH2) mpyrimidyl, wherein m=0, 1, or 2; Ar is a 5-10 membered monocyclic or bicyclic aromatic group optionally containing 1-4 ring heteroatoms independently selected from N, O, and S; or R1 and R2 together with the ring carbon atoms to which they are attached form a 5- or 6-membered fused ring, which may be saturated, unsaturated, or aromatic, and which independently contain 1 or 2 ring heteroatoms selected from the group consisting of O, N, and S. optionally containing heteroatoms, R' is selected from the group consisting of H, halogen, phenyl, 2-(N,N-dimethylamino)ethyl, CF3, OCl-C3 alkyl, and C1-C3 alkyl; R3 and R4 are independently varied and selected from the group consisting of H, CN, halogen, CF3, OCF3, OCl-C3 alkyl, and C1-C3 alkyl; X is O or S; Y is O or S; q=1 or 0; R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6=CH-C3-C6 cycloalkyl, CH=CR 6- C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar, and (CHR6) wand R is selected from the group consisting of CHAr, where w=0, 1, 2, or 3; Ar is a 5-10 membered monocyclic or bicyclic aromatic group optionally containing 1-4 ring heteroatoms independently selected from the group consisting of N, O, and S; R is selected from the group consisting of H or C-C alkyl; all cycloalkyl and cycloalkenyl optionally contain 1 or 2 ring heteroatoms independently selected from N, O, and S; and R, R, R′, R, R, R, R, and A are independently selected from the group consisting of H, C-C alkyl, and all cycloalkyl and cycloalkenyl optionally contain 1 or 2 ring heteroatoms independently selected from N, O, and S; All alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in r are optionally substituted with one or two substituents independently selected from C1-C3 alkyl, halogen, OH, OEt, OMe, CN, CH2F, OCF3, and CF3; and additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with a carbonyl group.

[0121] In further embodiments, R1 and R2 are independently varied and are selected from H, halogen, CF3, C1-C6 alkyl, C(=O)C1-C6 alkyl, C(=O)OC1-C6 alkyl, OC(=O)C1-C6 alkyl, OC1-C6 alkyl, SCH3, C3-C6 cycloalkyl, (CH2) m C3-C6 cycloalkyl, phenyl, pyridyl, pyrrolyl, thienyl, (CH2) m Phenyl, (CH2) m Pyrrolyl, and (CH2) m pyridyl, wherein the cycloalkyl group optionally contains one or two heteroatoms independently selected from the group consisting of O, N, and S; the alkyl, cycloalkyl, phenyl, pyrrolyl, and pyridyl groups are optionally substituted with one or two groups selected from halogen, methyl, ethyl, or trifluoromethyl; m is 0, 1, or 2; and R′ is selected from H, halogen, phenyl, 2-(N,N-dimethylamino)ethyl, CF 3、R3 and R4 are independently selected from the group consisting of H, halogen, CF 3、 X is O or S, Y is O or S, q=1 or 0, and R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6=CH-C3-C6 cycloalkyl, CH=CR 6- C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar, and (CHR7) w and R is selected from the group consisting of H and methyl; all cycloalkyl and cycloalkenyl groups in R optionally contain one or two ring heteroatoms independently selected from the group consisting of N, O, and S; and all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R, R, R, R, R, R, and Ar are independently substituted with one or two substituents selected from C-C alkyl, halogen, OEt, OMe, and trifluoromethyl.

[0122] In further embodiments, R1 and R2 are independently varied and are selected from H, halogen, CF3, C1-C6 alkyl, C(=O)C1-C6 alkyl, C(=O)OC1-C6 alkyl, OC(=O)C1-C6 alkyl, OC1-C6 alkyl, SCH3, (CH2) m Cyclopropyl, (CH2) m Cyclobutyl, (CH2) m Cyclopentyl, (CH2) m Cyclohexyl, (CH2) m Oxazolyl, (CH2) m Isoxazolyl, (CH2) m Thiazolyl, (CH2) m Isothiazolyl, (CH2) m Phenyl, (CH2) m Pyrrolyl, (CH2) m Pyridyl, and (CH2) m pyrimidyl, wherein the cyclopentyl and cyclohexyl groups optionally contain one or two ring heteroatoms independently selected from the group consisting of O, N, and S; the alkyl, cycloalkyl, phenyl, pyrrolyl, and pyridyl groups are optionally substituted with one or two groups independently selected from the group consisting of halogen, CH3, ethyl, and CF3; m is 0, 1, or 2; R' is selected from the group consisting of H, halogen, CF3, and C1-C3 alkyl; R3 and R4 are independently variable and are selected from the group consisting of H, halogen, CF 3、 OCF 3、 X is O or S, Y is O, q=1 or 0, and R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6=CH-C3-C6 cycloalkyl, CH=CR 6- C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar, and (CHR6) w and R is H or methyl; all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms independently selected from the group consisting of N, O, and S; and all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R, R, R, R, R, R, and Ar are independently substituted with one or two substituents selected from C-C alkyl, halogen, OMe, OEt, and CF.

[0123] In further embodiments, R1 and R2 are independently selected from the group consisting of H, halogen, CF3, OCl-C3 alkyl, C1-C6 alkyl, C(=O)OCl-C3 alkyl, OC(=O)C1-C3 alkyl, and C(=O)C1-C3 alkyl; R' is selected from the group consisting of H, F, CH3, and ethyl; R3 and R4 are independently selected from the group consisting of H, F, Cl, CF3, OCF3, OCl-C3 alkyl, and C1-C3 alkyl; and R5 is C1-C6 alkyl (CHR6). w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, or (CHR6) w Ar, CH2(CHR6) w Ar, or (CHR6) w CH2Ar.

[0124] In further embodiments, R2 is H or F, R' is H, R3 is selected from the group consisting of H, CH3, OCH3, CF3, OCF3, and Cl, R4 is selected from the group consisting of CH3, OCH3, CF3, OCF3, and Cl, and R5 is C3-C6 alkyl or (CH2) w It is a C3-C6 cycloalkyl.

[0125] In further embodiments, R1 is halogen or CF3, R2 is H or F, R' is H, and R3 and R4 are independently variable and include H, CH3, OCH 3、 CF 3、 OCF3, or Cl, and R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6=CH-C3-C6 cycloalkyl, CH=CR 6- C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar, and (CHR6) w CH2Ar.

[0126] In further embodiments, R1 is halogen or CF3, R2 is H or F, R' is H, and R3 and R4 are independently variable and include H, CH3, OCH 3、 CF 3、 OCF3, or Cl, and R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6=CH-C3-C6 cycloalkyl, CH=CR 6- C3-C6 cycloalkyl, (CHR6)w C5-C6 cycloalkenyl, CH2(CHR6) w C5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar, and (CHR6) w CH2Ar.

[0127] formula 4 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 4. Such compounds are described in U.S. Patent No. 8,293,911, issued October 23, 2012, and corresponding to U.S. Application No. 11 / 894,877, which is incorporated herein by reference in its entirety. In the event of any discrepancy in terminology relating to Formula 4, this reference, incorporated herein by reference, will control.

[0128] In embodiments, the Kv7 channel activator is a compound according to Formula 4: [ka] In the formula, R1 is H, halogen, CN, CH2CN, CF3, C1-C6 alkyl, OCH3, (C=O)OCH3, O(C=O)CH3, OCF3, (CH2) m R2 is selected from the group consisting of H, F, OCH3, CH3, and CF3; R3 and R4 are independently varied and selected from the group consisting of H, F, Cl, CF3, OCF3, OC1-C3 alkyl, or C1-C3 alkyl; R5 is C1-C6 alkyl, (CHR6) w C3-C6 cycloalkyl, (CHR6) w CH2C3~C6 cycloalkyl, CH2(CHR6) w C3-C6 cycloalkyl, CR6=CH-C3-C6 cycloalkyl, CH=CR 6- C3-C6 cycloalkyl, (CHR6) w C5-C6 cycloalkenyl, CH2(CHR6) wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar, (CHR6) w Ar, CH2(CHR6) w Ar, and (CHR6) w and R is selected from the group consisting of C1-C3 alkyl, halogen, cycloalkyl, aryl, and heteroaryl groups in R, R, R, R, R, R, and Ar, wherein w=0-3; Ar is phenyl, furyl, pyrrolyl, oxazolyl, thiazolyl, thienyl, or pyridyl; R is C1-C3 alkyl; and all alkyl, cycloalkyl, aryl, and heteroaryl groups in R, R, R, R, R, and Ar are optionally substituted with one or two substituents independently selected from C1-C3 alkyl, halogen, OCH, OCHCH, CN, and CF.

[0129] In other embodiments, R1 is selected from the group consisting of H, F, Cl, Br, CF3, C1-C6 alkyl, OCH3, CHOCH3, CH2CHOCH3, CHOCH2CH3, and OCH2CH3; R' is selected from the group consisting of H, CH3, CH2CH3, or halogen; R3 and R4 are independently varied and selected from the group consisting of H, F, Cl, CF3, OCF3, OCH3, and CH3; R5 is selected from the group consisting of C1-C6 alkyl, CH2C3-C6 cycloalkyl, CH2CH2C3-C6 cycloalkyl, CH=CH—C3-C6 cycloalkyl, CH=CH—C5-C6 cycloalkenyl, CH2C5-C6 cycloalkenyl, CH2CH2C5-C6 cycloalkenyl, C2-C6 alkenyl, and (CH2) w and Ar, wherein w=1 or 2; Ar is selected from the group consisting of phenyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, furyl, thienyl, pyrrolyl, and pyridyl; and all alkyl, cycloalkyl, aryl, and heteroaryl groups in R, R, R, R, R, and Ar are independently optionally substituted with 1 or 2 substituents selected from the group consisting of CH, halogen, OCH, OCHCH, CN, and CF.

[0130] In other embodiments, R1 is selected from the group consisting of H, F, Cl, Br, CF3, C1-C6 alkyl, OCH3, CHOCH3, CH2CHOCH3, CHOCH2CH3, and OCH2CH3; R' is selected from the group consisting of H, CH3, CH2CH3, or halogen; R3 and R4 are independently varied and selected from the group consisting of H, F, Cl, CF3, OCF3, OCH3, and CH3; R5 is selected from the group consisting of C1-C6 alkyl, CH2C3-C6 cycloalkyl, CH2CH2C3-C6 cycloalkyl, CH=CH—C3-C6 cycloalkyl, CH=CH—C5-C6 cycloalkenyl, CH2C5-C6 cycloalkenyl, CH2CH2C5-C6 cycloalkenyl, C2-C6 alkenyl, and (CH2) w and Ar, wherein w=1 or 2; Ar is selected from the group consisting of phenyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, furyl, thienyl, pyrrolyl, and pyridyl; and all alkyl, cycloalkyl, aryl, and heteroaryl groups in R, R, R, R, R, and Ar are independently optionally substituted with 1 or 2 substituents selected from the group consisting of CH, halogen, OCH, OCHCH, CN, and CF. wherein R1 is selected from the group consisting of F, CF3, Cl, CH3, CH2CH3, SCH3, OCH3, CHOCH3, CHOCH2CH3, OCF3, phenyl, thienyl, and H; R2 is selected from the group consisting of H, F, Cl, and OCH3; R' is selected from the group consisting of H, F, CH2CH3, and CH3; R3 and R4 are independently varied and are selected from the group consisting of H, Cl, CH3, CF3, OCH3, and OCF3; R5 is C4-C6 alkyl, (CH2) w Ar, and (CH2) w C5-C6 cycloalkyl, wherein w is 1, 2, or 3.

[0131] In other embodiments, R1 is selected from the group consisting of F, CF3, Cl, CH3, OCH3, CHOCH3, and H; R2 is selected from the group consisting of H, F, CH3, and Cl; R' is H; R3 is selected from the group consisting of H, Cl, CH3, CF3, OCH3, and OCF3; R4 is selected from the group consisting of Cl, OCH3, and CH3; and R5 is C-C alkyl or 2-cyclopentylethyl.

[0132] In other embodiments, R3 and R4 are both CH3 or both OCH3, and R5 is C5-C6 alkyl.

[0133] In other embodiments, R′ and R2 are H, R3 and R4 are both methyl, and R5 is C5-C6 alkyl or (CH2) w C5-C6 cycloalkyl, where w is 1, 2, or 3.

[0134] In other embodiments, the compound is 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-methylphenyl]-3,3-dimethylbutanamide, N-[2-chloro-4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethylphenyl]-3-cyclopentylpropionamide, N-[2,6-dimethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinoline- 2-yl)-phenyl]-3,3-dimethylbutanamide, N-[2-chloro-6-trifluoromethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide, N-[2-chloro-4-(6-chloro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethylphenyl]-3,3-dimethylbutanamide, N-[4-(6-chloro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethyl-phenyl]-3,3-dimethylbutanamide Chilbutanamide, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-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- 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] N-[4-(3,4-dihydro-1H-isoquinolin-2-yl)-2-methoxy-6-methyl-phenyl]-3,3-dimethylbutanamide, N-[2-chloro-4-(3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethoxy-phenyl]-3,3-dimethylbutanamide, N-[4-(3,4-dihydro-M-isoquinolin-2-yl)-2,6-dimethoxy-phenyl]-3,3-dimethylbutanamide, N-[2,6-dimethyl-4-(7-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide, N-[2,6-dimethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethyl-thiobutanamide, [2,6-dimethyl-4-(6-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-carbamic acid ethyl ester, and N-[2,6-dimethyl-4-(7-trifluoromethyl-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-3,3-dimethylbutanamide.

[0135] formula 5 In another embodiment, the Kv7 channel activator may be selected from one of the following compounds: Such compounds are described in U.S. Patent No. 8,993,593, issued March 31, 2015, corresponding to U.S. Application No. 12 / 698,070, filed February 1, 2010, and U.S. Publication No. US20220265634A1, published August 25, 2022, corresponding to U.S. Application No. 17 / 668,340, filed February 9, 2022, which are incorporated herein by reference in their entireties. In the event of any discrepancy in terminology relating to Formula 5, these references, incorporated herein by reference, shall control.

[0136] In embodiments, the Kv7 channel activator is a compound according to formula 5: [ka] Optionally, the compound is substituted at any position.

[0137] formula 6 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 event of any discrepancy in terminology relating to Formula 6, these references, incorporated herein by reference, shall control. [ka] Or optionally, the compound is substituted at any position.

[0138] formula 7 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 7: Such compounds are described in U.S. Patent No. 10,526,328, issued January 7, 2020, corresponding to U.S. Application No. 16 / 124,853, filed September 7, 2018; U.S. Patent No. 10,106,536, issued October 23, 2018, corresponding to U.S. Application No. 15 / 591,844, filed May 10, 2017; U.S. Patent No. 9,650,376, issued May 16, 2017, corresponding to U.S. Application No. 14 / 776,271, filed March 17, 2014; and U.S. Publication No. US20220060208A1, published February 24, 2022, corresponding to U.S. Application No. 17 / 277,145, filed January 14, 2019, which are incorporated by reference in their entireties herein. In the event of any discrepancy in terminology relating to Formula 7, these references, which are incorporated herein by reference, will control.

[0139] In embodiments, the Kv7 channel activator is a compound according to Formula 7: [ka] where L is CH2 and R 1 is an optionally substituted cyclic C3H5, and R 1 The optional substituent of is CF3, and R 2 is an optionally substituted cyclobutyl, and R 3 is an optionally substituted C alkyl, and R 3 The optional substituents of are OH and R 4 is H and R 5 is H or or where L is CH2 and R 1 is an optionally substituted C alkyl, and R1 The optional substituents of R are CF or CH, 2 is an optionally substituted cyclobutyl, and R 3 is an optionally substituted C alkyl, and R 3 The optional substituents of are OH and R 4 is H and R 5 is H or or In the formula, L is CH2, CF2, CHCH3, CH2CH2, C3H6, CH2O, C2H4O, or C3H6O, and O in CH2O, C2H4O, or C3H6O is R 1 and R 1 is an optionally substituted C 1~2 Alkyl, optionally substituted C 5~10 Cycloalkyl, optionally substituted C 1~12- O-alkyl, optionally substituted C 6~10 Aryl, optionally substituted C 6~10- O-aryl or optionally substituted C 2~9 heterocyclyl, and R 1 The optional substituents of are independently R A , F, Cl, CN, OR A , CF3, NR A R B , C.O.R. A , CO2R A ,OCOR A , N.R. A COR B ,CONR A R B and R A and R B are independently H or C 1~12 alkyl, and R 2 is an optionally substituted C 2~4 Acyclic aryl, optionally substituted cyclobutyl, optionally substituted C 6~10 Aryl or optionally substituted C 2~9 heterocyclyl, and R 2 The optional substituents are independently F, Cl, Br, I, CN, C1~6 Alkyl, C 1~6- O-Alkyl, C 1~6 Alkylamines, C 1~6 Aminoalkyl, C 1~6 Aminoacyl, C 1~6 Alkylthio or C 1~6 alkylsulfonyl, and R 3 , R 4 , and R 5 are independently H, F, Cl, Br, I, CN, optionally substituted C 1~12 Alkyl, optionally substituted C 1~12- O-alkyl, optionally substituted C 2~9 Heterocyclyl, optionally substituted C 6~10 Aryl, optionally substituted C 2~9- O-heterocyclyl, optionally substituted C 6~10 O-aryl, optionally substituted C 1~12 Acylamino, optionally substituted C 1~12 Aminoacyl or optionally substituted C 1~12 aminoalkyl, and R 3 , R 4 , or R 5 The optional substituents are independently F, Cl, Br, I, CN, C 1~6 Alkyl, C 1~6- O-Alkyl, C 1~6 Alkylamines, C 1~6 Aminoalkyl, C 1~6 Aminoacyl, C 1~6 Acylamino, C 1~6 Alkylthio or C 1~6 It is alkylsulfonyl.

[0140] In a further embodiment, R 2 is an optionally substituted CH, an optionally substituted cyclobutyl, an optionally substituted C 6~10 aryl, or optionally substituted C 2~9 It is a heterocyclyl.

[0141] In a further embodiment, R2 is optionally substituted C4H9 or optionally substituted cyclobutyl.

[0142] In a further embodiment, R 2 is optionally substituted phenyl or optionally substituted C 2~9 It is a heterocyclyl.

[0143] In a further embodiment, R 1 is optionally substituted phenyl.

[0144] In a further embodiment, R 1 is optionally substituted phenyl.

[0145] In a further embodiment, R 1 is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0146] In a further embodiment, R 1 is C 2~4- It is O-alkyl.

[0147] In a further embodiment, R 1 is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl.

[0148] In a further embodiment, R 1 is selected from the group consisting of: [ka]

[0149] In a further embodiment, R 2 is selected from the group consisting of: [ka]

[0150] In a further embodiment, R3 is CF3, Cl, CN, OCH3, or H.

[0151] In a further embodiment, R 1 is selected from the group consisting of: [ka]

[0152] In a further embodiment, R 4 is CH3, CF3, Cl, or H.

[0153] In a further embodiment, R 2 is selected from the group consisting of: [ka]

[0154] In a further embodiment, the Kv7 channel activator is selected from the group consisting of: [ka] [ka] [ka] [ka] [ka]

[0155] In a further embodiment, the Kv7 channel activator is selected from the group consisting of: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0156] formula 8 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 8. Such compounds are described in U.S. Patent No. 9,650,376, which corresponds to U.S. Application No. 14 / 776,271, published February 4, 2014, filed March 17, 2014, and which is incorporated herein by reference in its entirety. In the event of any discrepancy in terminology relating to Formula 8, this reference, incorporated herein by reference, will control.

[0157] In embodiments, the Kv7 channel activator is a compound according to Formula 8: [ka] In the formula, L is CH2, CF2, CHCH3, CH2CH2, C3H6, CH2O, C2H4O, or C3H6O, and O in CH2O, C2H4O, or C3H6O is R 1 and R 1is an optionally substituted C 1~2 Alkyl, optionally substituted C 5~10 Cycloalkyl, optionally substituted C 1~-12- O-alkyl, optionally substituted C 6~10 Aryl, optionally substituted C 6~10- O-aryl or optionally substituted C 2~9 heterocyclyl, and R 1 The optional substituents of are independently R A , F, Cl, CN, OR A , CF3, NR A R B , C.O.R. A , CO2R A ,OCOR A , N.R. A COR B ,CONR A R B and R A and R B are independently H or C 1~12 alkyl, and R 2 is an optionally substituted C 2~4 Acyclic aryl, optionally substituted cyclobutyl, optionally substituted C 6~10 aryl, or optionally substituted C 2~9 heterocyclyl, and R 2 The optional substituents are independently F, Cl, Br, I, CN, C 1~6 Alkyl, C 1~6- O-Alkyl, C 1~6 Alkylamines, C 1~6 Aminoalkyl, C 1~6 Aminoacyl, C 1~6 Alkylthio, or C 1~6 alkylsulfonyl, and R 3 , R 4 , and R 5 are independently H, F, Cl, Br, I, CN, optionally substituted C 1~12 Alkyl, optionally substituted C 1~12- O-alkyl, optionally substituted C 2~9 Heterocyclyl, optionally substituted C6~10 Aryl, optionally substituted C 2~9- O-heterocyclyl, optionally substituted C 6~10 O-aryl, optionally substituted C 1~12 Acylamino, optionally substituted C 1~12 aminoacyl, or optionally substituted C 1~12 aminoalkyl, and R 3 , R 4 , or R 5 The optional substituents are independently F, Cl, Br, I, CN, C 1~6 Alkyl, C 1~6- O-Alkyl, C 1~6 Alkylamines, C 1~6 Aminoalkyl, C 1~6 Aminoacyl, C 1~6 Acylamino, C 1~6 Alkylthio, or C 1~6 It is alkylsulfonyl.

[0158] In a further embodiment, R 2 is an optionally substituted CH, an optionally substituted cyclobutyl, an optionally substituted C 6~10 aryl, or optionally substituted C 2~9 It is a heterocyclyl.

[0159] In a further embodiment, R 2 is optionally substituted C4H9 or optionally substituted cyclobutyl.

[0160] In a further embodiment, R 2 is optionally substituted phenyl or optionally substituted C 2~9 It is a heterocyclyl.

[0161] In a further embodiment, R 1 is optionally substituted phenyl.

[0162] In a further embodiment, R 1 is optionally substituted phenyl.

[0163] In a further embodiment, R 1 is optionally substituted cyclopentyl or optionally substituted cyclohexyl.

[0164] In a further embodiment, R 1 is C 2~4- It is O-alkyl.

[0165] In a further embodiment, R 1 is optionally substituted tetrahydrofuranyl or optionally substituted tetrahydro-2H-pyranyl.

[0166] In a further embodiment, R 1 is selected from the group consisting of: [ka]

[0167] In a further embodiment, R 2 is selected from the group consisting of: [ka]

[0168] In a further embodiment, R 3 is CF3, Cl, CN, OCH3, or H.

[0169] In a further embodiment, R 1 is selected from the group consisting of: [ka]

[0170] In a further embodiment, R 4 is CH3, CF3, Cl, or H.

[0171] In a further embodiment, R 2is selected from the group consisting of: [ka]

[0172] formula 9 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 9. Such compounds are disclosed in International Publication No. WO2021023616A1, published February 11, 2021, corresponding to International Application No. PCT / EP2020 / 071514, filed July 30, 2020; International Publication No. WO2019161877A1, published August 29, 2019, corresponding to International Application No. PCT / EP2018 / 054057, filed February 20, 2018; and International Publication No. WO2019161877A1, published September 8, 2022, corresponding to International Application No. PCT / EP2018 / 054057, filed September 8, 2022, which are incorporated herein by reference in their entireties. US Publication No. US20220280455A1, which corresponds to US Application No. 17 / 631,762, filed July 30, 2020; US Publication No. US20210032196A1, which corresponds to US Application No. 16 / 943,872, filed July 30, 2020, published February 4, 2021; US ​​Publication No. US20210032196A1, which corresponds to US Application No. 16 / 943,872, filed July 30, 2020. In the event of any discrepancy in terminology relating to Formula 9, these references, incorporated herein by reference, shall control.

[0173] In embodiments, the Kv7 channel activator is a compound according to Formula 9: [ka] wherein R1 is selected from the group consisting of C1-C6 alkyl, CF3, CH2CF3, CF2CHF2, and C3-C8 cycloalkyl, which C3-C8 cycloalkyl can be substituted with one or two substituents selected from the group consisting of C1-C3 alkyl, F, CHF2, and CF3; R2 is H, C1-C6 alkyl, or CF3; or R1 and R2 combine to form a C3-C5 cycloalkyl optionally substituted with one or two F, CHF2, or CF3; and R3 is C1-C3 alkyl or CHO-C 1~3 alkyl, and the C1-C3 alkyl or CH2O—C 1~3 The alkyl is optionally substituted with C≡N, 3F, or C3-C5 cycloalkyl, and R4 is selected from the group consisting of OCF3 or OCHF2.

[0174] In a further embodiment, R4 is OCF3 or OCHF2.

[0175] In a further embodiment, R3 is CH 2- O-CF3, CH 2- O-cyclopropyl, CH 2- C≡N.

[0176] In further embodiments, R1 is C3-C4 cycloalkyl optionally substituted with one or two C1-C3 alkyl, F, CHF2, or CF3.

[0177] In a further embodiment, R1 and R2 combine to form a cyclobutyl optionally substituted with one or two F, and R4 is OCF3 or OCHF2.

[0178] In a further embodiment, the Kv7 channel activator is (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.

[0179] In a further embodiment, the Kv7 channel activator is (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 amide, (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-(trifluoromethyl)cyclopropyl)propanamide -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)phenyl)ethyl (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-(difluoro (S)-N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(1-fluorocyclopropyl)-3-hydroxybutanamide, (S)-N-((R)-2-(difluoromethoxy)-1-(3-(trifluoromethoxy)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 amide, (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.

[0180] In a further embodiment, the Kv7 channel activator is a compound according to formula 8, wherein R 1 is selected from the group consisting of C1-C6 alkyl, CF3, CH2CF3, CF2CHF2, and C3-C8 cycloalkyl, wherein the C3-C8 cycloalkyl can be substituted with one or two F, CHF2, or CF3; R 2 is H, C1-C6 alkyl, or CF3, or R1 and R 2 combine to form a C-C cycloalkyl optionally substituted with one or two F, CHF, or CF, and R 3 is C1-C3 alkyl or CHO-C 1~3 alkyl, and the C1-C3 alkyl or CH2O—C 1~3 The alkyl may be optionally substituted with one or two F, and R 4 is selected from the group consisting of OCF3, OCH2CF3, or OCHF2.

[0181] In a further embodiment, R 4 is OCF3 or OCHF2.

[0182] In a further embodiment, R 2 is H or CH3.

[0183] In a further embodiment, R 3 is CHO-C 1~3 It is alkyl.

[0184] In a further embodiment, R 1 is a C3-C4 cycloalkyl optionally substituted with one or two F, CHF2, or CF3.

[0185] In a further embodiment, R 1 is t-butyl, and R 2 is H and R 4 is OCF3, OCH2CF3, OCHF2, or CF3.

[0186] In a further embodiment, R 1 and R 2 combine to form a cyclobutyl optionally substituted with one or two F, and R 4 is OCF3, OCH2CF3, OCHF2, or CF3.

[0187] In a further embodiment, the Kv7 channel activator is (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-[(1S)-1-[3-(trifluoromethoxy)phenyl]ethyl]pentanamide, hydroxy-4,4-dimethyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)pentanamide, (S)-N-((S)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide, (R)-N-((S)-1-(3-(difluoromethoxy)phenyl)ethyl)-3-hydroxy-4,4-dimethylpentanamide, (S)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethyl) )phenyl)ethyl)pentanamide, (R)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethyl)phenyl)ethyl)pentanamide, (S)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)propyl)pentanamide, (R)-3-hydroxy-4,4-dimethyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)propyl)pentanamide, (S)-3-(3,3-difluorocyclobutene (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-(trifluoromethoxy)phenyl)ethyl)propanamide, (R)-3-(1-(difluoromethyl)cyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)propanamide, (R)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl)-3-(1-(trifluoromethyl)cyclopropyl) (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)pentanamide, 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-(trifluoromethoxy)phenyl)ethyl)pentanamide, (R)-3-(1-fluorocyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoromethoxy)phenyl)ethyl) Butanamide, (S)-3-(1-fluorocyclopropyl)-3-hydroxy-N-((S)-1-(3-(trifluoro-methoxy)phenyl)ethyl)butanamide, (R)-2-(1-hydroxycyclopentyl)-N-(2-methoxy-1-(3-(trifluoromethoxy)phenyl)ethyl)acetamide, (R)-3-cyclopropyl-3-hydroxy-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide, (S)-3-cyclopropyl-3-hydroxy-N-(( (S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide, (R)-4,4,4-trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide, and (S)-4,4,4-trifluoro-3-hydroxy-3-methyl-N-((S)-1-(3-(2,2,2-trifluoroethoxy)phenyl)ethyl)butanamide, or a pharmaceutically acceptable salt of any of these compounds.

[0188] Formula 10 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 10. Such compounds are disclosed in International Publication No. WO2009015667A1, which corresponds to International Application No. PCT / DK2008 / 050191, published February 5, 2009, filed July 31, 2008, and International Application No. PCT / DK2003 / 000906, published July 15, 2004, filed December 18, 2003, which are incorporated herein by reference in their entireties. No. 7,368,472, published May 6, 2008, which corresponds to U.S. application Ser. No. 10 / 540,075, filed December 18, 2003; and U.S. Publication No. US20100256145A1, published October 7, 2010, which corresponds to U.S. application Ser. No. 12 / 671,505, filed July 31, 2008. In the event of any discrepancy in terminology relating to Formula 8, these references, which are incorporated herein by reference, control.

[0189] In embodiments, the Kv7 channel activator is a compound according to Formula 10: [ka] In the formula, R 1 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl), and R 2 and R 2′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), aryl-C 1-6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl), and R 3 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -cycloalkyl(alkenyl), NR 10 R 10′- C 1~4 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 3~8 -Cycloalkyl(alkenyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl), and R 10 and R 10′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 10 and R 10′ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, X is CO or SO2, and Z is O or NR 4 and R 4 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1-6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl) or R 3 and R 4 together with the nitrogen atom to which they are attached form a 4- to 8-membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, and R 3 and R 4 and the ring formed by the nitrogen atom is independently selected from C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and aryl-C 1~6 - alkyl(alkenyl / alkynyl), q is 0 or 1 and Y is heteroaryl of one of the following formulae: [ka] 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 R 5 But independently, C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, halogen, halo-C 1-6 -Alkyl(alkenyl / alkynyl), alkyl(alkenyl / alkynyl)oxy, -CO-NR 6 R 6′ , cyano, nitro, -NR 7 R 4′ , -SR 8 , -SO2R 8 , and SO2OR 8 and R 6 and R 6′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / alkynyl), and aryl; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), aryl, and acyl; R 8 But C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Cycloalkyl(alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), or a pharmaceutically acceptable salt thereof.

[0190] In a further embodiment, the Kv7 channel activator is {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 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.

[0191] In a further embodiment, the Kv7 channel activator is a compound according to the formula: [ka] or a pharmaceutically acceptable salt thereof.

[0192] In a further embodiment, the Kv7 channel activator is 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.

[0193] In a further embodiment, the Kv7 channel activator is a compound according to formula 10, wherein R 1 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl), and R 2 and R 2′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C1-6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl), and R 3 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -cycloalkyl(alkenyl), NR 10 R 10′- C 1~6 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 3~8 -Cycloalkyl(alkenyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl), and R 10 and R 10′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 10 and R 10′ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, X is CO or SO2, and Z is O or NR 4 and R 4 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1-6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalkyl(alkenyl) or R 3 and R 4 together with the nitrogen atom to which they are attached form a 4- to 8-membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, and R 3 and R 4 and the ring formed by the nitrogen atom is independently selected from C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and aryl-C 1~6 -alkyl(alkenyl / alkynyl), q is 0 or 1, and Y is heteroaryl of the formula: [ka] represents 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 R 5 But independently, C1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, halogen, halo-C 1-6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, -CO-NR 6 R 6′ , cyano, nitro, -NR 7 R 7′ , S.R. 8 , -SO2R 8 , and SO2OR 8 and R 6 and R 6′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / alkynyl), and aryl; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), aryl, and acyl; R 8 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), or a pharmaceutically acceptable salt thereof.

[0194] In a further embodiment, R 1 is hydrogen and C 1~6 - alkyl(alkenyl / alkynyl).

[0195] In a further embodiment, the substituent R 2 and R 2′ At least one of is a hydrogen atom.

[0196] In a further embodiment, R 2 and R 2′ are hydrogen atoms.

[0197] In a further embodiment, X is CO.

[0198] In a further embodiment, q is 0.

[0199] In a further embodiment, q is 1 and Z is an oxygen atom.

[0200] In a further embodiment, R 3 is C 1~6 -Alkyl(alkenyl / alkynyl) and aryl-C 1~6 - alkyl(alkenyl / alkynyl).

[0201] In a further embodiment, R 3 is C 1~6 -Alkyl (alkenyl / alkynyl).

[0202] In a further embodiment, R 3 is aryl-C 1~6-Alkyl (alkenyl / alkynyl).

[0203] In a further embodiment, W is a sulfur atom.

[0204] In a further embodiment, Y is of the formula: [ka] 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 R 5 independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, halogen, halo-C 1-6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, -CO-NR 6 R 6′ , cyano, nitro, -NR 7 R 7′ , S.R. 8 , -SO2R 8 , and SO2OR 8 and R 6 and R 6′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / alkynyl), and aryl; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C1~6 - selected from the group consisting of alkyl(en / ynyl), aryl, and acyl; R 8 is C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and -NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl).

[0205] In a further embodiment, Y is of the formula: [ka] 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 R 5 independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), aryl, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, halogen, halo-C 1-6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, -CO-NR 6 R 6′ , cyano, nitro, -NR 7 R 7′ , S.R. 8 , -SO2R 8 , and SO2OR8 and R 6 and R 6′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / alkynyl), and aryl; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), aryl, and acyl; R 8 is C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and -NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl).

[0206] Formula 11 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 11. Such compounds are disclosed in International Publication No. WO2009015667A1, which corresponds to International Application No. PCT / DK2008 / 050191 published on February 5, 2009, and filed on July 31, 2008; International Publication No. WO2004058739A1, which corresponds to International Application No. PCT / DK2003 / 000906 published on July 15, 2004, and filed on December 18, 2003; and U.S. Patent No. 7,333,437, which corresponds to U.S. Application No. 10 / 540,075 published on May 6, 2008, and filed on December 18, 2003, which are incorporated herein by reference in their entireties. No. 68,472, U.S. Publication No. US20100256145A1, published October 7, 2010, corresponding to U.S. Application No. 12 / 671,505, filed July 31, 2008, International Publication No. WO2004082677A1, published September 30, 2004, corresponding to International Application No. PCT / DK2004 / 000186, filed March 18, 2004, and International Publication No. WO2004080950A1, published or issued September 23, 2004, corresponding to International Application No. PCT / DK2004 / 000162, filed March 12, 2004. In the event of any discrepancy in terminology relating to Formula 11, these references, incorporated herein by reference, control.

[0207] In embodiments, the Kv7 channel activator is a compound according to Formula 11, [ka] In the formula, s is 0 or 1, and U is O, S, SO2, SO2NR 11 , CO-O, or CONR 11 and R 11 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), or R2 and R 11 But R 11 together with the nitrogen atom to which it is attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 additional heteroatoms, q is 0 or 1, X is CO or SO2 with the proviso that when X is SO2, q is 0, Z is O or S, and R 1 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 2 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8-Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 1~6 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 3~8 -cycloalkyl(alkenyl), and NR 10 R 10′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 10 and R 10′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 10 and R 10′ together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 2 is halogen or cyano, s is 0, s is 1, and R 2 is a hydrogen atom or acyl, provided that U is O or S, and R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), heterocycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), heterocycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -cycloalkyl(alkenyl), Ar-heterocycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-heterocycloalkyl(alkenyl), Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-heterocycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 1~6-Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-heterocycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-Ar, Halo-C 3~8 -Cycloalkyl(alkenyl)-Ar, halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)-Ar, Halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl)-Ar, Cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-heterocycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), acyl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 3~8 -Cycloalkyl(alkenyl), acyl-heterocycloalkyl(alkenyl), acyl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 1~6-Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), NR 12 R 12′ , optionally substituted NR 12 R 12′- C 1~6 -Alkyl(alkenyl / alkynyl), optionally substituted NR 12 R 12′- C 3~8 -cyclo(alkenyl) and optionally substituted NR 12 R 12′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 12 and R 12′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl) Ar-heterocycloalkyl(alkenyl), Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar-oxy-heterocycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8-Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 12 and R 12′ together with the nitrogen atom to which they are attached form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 3 NR 12 R 12′ provided that q is 0, and Y is a group of the formula: [ka] represents wherein the line represents a bond connecting the group represented by Y to a carbon atom, W is O or S, V is N, C, or CH, T is N, NH, or O, a is 0, 1, 2, or 3, b is 0, 1, 2, 3, or 4, c is 0 or 1, d is 0, 1, 2, or 3, e is 0, 1, or 2, f is 0, 1, 2, 3, 4, or 5, g is 0, 1, 2, 3, or 4, h is 0, 1, 2, or 3, j is 0, 1, or 2, and k is 0, 1, 2, or 3; and each R 5 But independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6-Alkyl (alkenyl / alkynyl), Ar-C 3~8 -cycloalkenyl, Ar-cycloalkenyl-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy, Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-carbonyl, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl)oxy, halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -CO-NR 6 R 6′ , cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 7 R 7′ , S.R. 8 , and SO2R 8 or two adjacent R 5 together with the aromatic group form a 5- to 8-membered ring optionally containing one or two heteroatoms, and R 6 and R 6′ are independently hydrogen, C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(en / ynyl), and Ar; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, Heterocycloalkenyl-C 1~6 -Alkyl(alkenyl / alkynyl), heterocycloalkyl(alkenyl)-C 3~8 -Cycloalkyl(alkenyl), heterocycloalkyl(alkenyl)-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - is selected from the group consisting of alkyl(ken / ynyl), heterocycloalk(en)yl-Ar, and acyl, or R 7 and R 7′ together with the nitrogen atom to which they are attached form a 5- to 8-membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, and R 8 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Alkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, and -NR 9 R 9′ and R 9 and R 9′′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Alkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6-alkyl(alkenyl / alkynyl), or a pharmaceutically acceptable salt thereof.

[0208] In a further embodiment, the Kv7 channel activator is {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 esters, [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 propyl ester, {4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methoxy-phenyl}-carbamic acid {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 ethyl ester, [2-cyclopentyloxy-4-(3-fluoro-2-methylbenzylamino)-phenyl yl]-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-methylphenyl}-carbamic acid propyl ester, {4-[(4-isopropylbenzyl)-(methyl)amino]-2-methylphenyl}-carbamic acid propyl ester, {2-methyl-4-[methyl-(4-trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester,{2-methyl-4-[methyl-(4-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 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 methyl-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 phenyl)-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)-( {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-ylmethylamino]-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- [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, phenyl}-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 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}-amideN-{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-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-phenylacetamide, 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}-3,3-dimethylbutyramide, N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}- phenyl}-butylamide, 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-methoxyphenyl)-acetamide -phenyl}-2-(4-fluorophenyl)-acetamide, 2,3-dihydro-benzo[1,4]dioxin-6-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide, 2,3-dihydro-benzofuran-5-carboxylic acid {2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-amide, N-{2-chloro-4-[(5-chloro-thiophen-2-ylmethyl)-amino]-phenyl}-3-cyclohexylpropionamide, N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2,2-dimethylpropionamide, N-{4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-2-methyl-phenyl}-2-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-methylphenyl}-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 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]thiophene -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-phenylamino)-methyl]-benzoic acid methyl ester, N-[2-methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-2-morpholin-4-yl-acetamide, 2,2-dimethyl-N-{2-methyl-4-[(3-methyl-5-phenylisoxazo N-{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.

[0209] In a further embodiment, the Kv7 channel activator is a compound according to formula 11, wherein s is 0 or 1 and U is O, S, SO2, SONR 11 , or CONR 11 and R 11 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), or C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl) or R 2 and R 11 together with the nitrogen atom form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2 or 3 further heteroatoms, q is 0 or 1, X is CO or SO2 with the proviso that when X is SO2, q is 0, Z is O or S, and R 1 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -cycloalkyl(alkenyl), or cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), and R2 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 Cycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 1~6 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 3~8 -cycloalkyl(alkenyl), or NR 10 R 10′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), and R 10 and R 10′ are each independently hydrogen, C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -cycloalkyl(alkenyl) or cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl) or R 10 and R 10′ together with the nitrogen atom form a 5-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 2 is halogen or cyano, s is 0, s is 1, and R 2 is a hydrogen atom or acyl, provided that U is O or S, and R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), heterocycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), C 1~6-Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), heterocycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-heterocycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-heterocycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-heterocycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-heterocycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), acyl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 3~8 -Cycloalkyl(alkenyl), acyl-heterocycloalkyl(alkenyl), acyl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), NR 12 R 12′ , optionally substituted NR 12 R 12′ -C 1~6 -Alkyl(alkenyl / alkynyl), optionally substituted NR 12 R 12′ -C 3~8 -cycloalkyl(alkenyl), or optionally substituted NR 12 R 12′ -C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), and R 12and R 12′ are each independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar-heterocycloalkyl(alkenyl), Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar-oxy-heterocycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -cycloalkyl(alkenyl) or cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl) or R 12 and R 12′ But together with the nitrogen atom, , forming a 5-8 membered saturated or unsaturated ring optionally containing two or three additional heteroatoms, with the proviso that R 3 NR 12 R 12′ provided that q is 0, and Y is a group of the formula: [ka] and where "|" represents a bond connecting the group represented by Y to a carbon atom, V is C or CH, k is 0, 1, 2, or 3, and each R 5 But independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy, Ar-oxy-C 1~6 Alkyl (alkenyl / alkynyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), Ar-oxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 1~6 -Alkyl(alkenyl / alkynyl)-carbonyl, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -CO-NR 6 R 6′ , cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 7 R 7′ , S.R. 8 , or SO2R 8 or two adjacent R 5 group, together with the aromatic group, forms a 5- to 8-membered ring optionally containing one or two heteroatoms, R 6 and R 6′ are each independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), or Ar, and R 7 and R 7′ are each independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, Heterocycloalkenyl-C 1~6 -Alkyl(alkenyl / alkynyl), heterocycloalkyl(alkenyl)-C 3~8 -Cycloalkyl(alkenyl), heterocycloalkyl(alkenyl)-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(en / ynyl), heterocycloalk(en)yl-Ar, or acyl, or R 7 and R7′ together with the nitrogen atom form a 5- to 8-membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, and R 8 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, or -NR 9 R 9′ and R 9 and R 9′ are each independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), or C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), or a salt thereof.

[0210] In a further embodiment, R 1 is C 1~6 - alkyl (alkenyl / alkynyl) or hydrogen.

[0211] In a further embodiment, s is 0.

[0212] In a further embodiment, s is 1.

[0213] In a further embodiment, U is an oxygen atom.

[0214] In a further embodiment, R 2 is hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), halogen, halo-C 1~6 -alkyl(alkenyl / alkynyl), or cyano, provided that R 2 is halogen or cyano, s is 0, s is 1, and R2 is a hydrogen atom, provided that U is O or S.

[0215] In a further embodiment, Z is an oxygen atom.

[0216] In a further embodiment, Z is a sulfur atom.

[0217] In a further embodiment, q is 0.

[0218] In a further embodiment, q is 1.

[0219] In a further embodiment, X is CO.

[0220] In a further embodiment, R 3 is C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), heterocycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), heterocycloalkyl (alkenyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), NR 12 R 12′ , optionally substituted NR 12 R 12′- C 1~6 -alkyl(alkenyl / alkynyl), or optionally substituted NR 12 R 12′- C3~8 -cycloalkyl(alkenyl).

[0221] In a further embodiment, R 12 and R 12′ are each independently hydrogen, C 1~6 -Alkyl(alkenyl / alkynyl), or Ar.

[0222] In a further embodiment, V is CH.

[0223] In further embodiments, each R 5 independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), Ar, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, Ar-oxy, C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), NR 7 R 7′ , S.R. 8 , or SO2R 8 or two adjacent R 5 The group, together with the aromatic group, forms a 5- to 8-membered ring optionally containing one or two heteroatoms.

[0224] In a further embodiment, R 7 and R 7′ Both are C 1~6 -Alkyl (alkenyl / alkynyl).

[0225] In a further embodiment, R 8 is C 1~6 -alkyl(alkenyl / alkynyl) or Ar.

[0226] In a further embodiment, the Kv7 channel activator is 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-trifluoromethyl ... N-(4-{[6-(4-cyanophenoxy)-pyridin-3-ylmethyl]-amino}-2-methylphenyl)-2-(4-fluorophenyl)-acetamide, N-{4-[(6-chloropyridin-3-ylmethyl)-amino]-2-methylphenyl}-2-(4-fluorophenyl)-acetamide, or 2,2-dimethyl-N-{2-methyl-4-[(6-phenoxypyridin-3-ylmethyl)-amino]-phenyl}-propionamide, or a salt thereof.

[0227] In a further embodiment, the Kv7 channel activator is a compound according to formula 11, wherein U is O, S, or NR 2′ where X is CO or SO2 and Z is O, S, or NR 4 and R 4 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cyclo(alkenyl), q is 0 or 1, and R 1 and R 1′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8-Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl), and halo-C 3~8 -cycloalkyl(alkenyl), and R 2 But hydrogen, halogens, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -cycloalkyl(alkenyl), and cyano, provided that R 2 is halogen or cyano, s is 0, s is 1, and U is NR 2′ If R 2′ But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C1~6 -Alkyl(alkenyl / alkynyl), and halo-C 3~8 -cycloalkyl(alkenyl), or R 2 and R 2′ together form a 5- to 8-membered saturated or unsaturated ring optionally containing one further heteroatom, and R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl), and halo-C 3~8 -cycloalkyl(alkenyl), and Y is selected from the group consisting of: [ka] wherein the line represents a bond connecting the group represented by Y to the nitrogen atom; W is O or S; a is 0, 1, 2, or 3; b is 0, 1, 2, 3, or 4; c is 0 or 1; d is 0, 1, 2, or 3; e is 0, 1, or 2; f is 0, 1, 2, 3, 4, or 5; g is 0, 1, 2, 3, or 4; h is 0, 1, 2, or 3; and j is 0, 1, 2, or 3. 5 But independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), Ar, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, C1~6 -Alkyl(alkanyl / alkenyl / alkynyl)oxy, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), -CO-NR 6 R 6′ , cyano, nitro, -NR 7 R 7′ , -SR 8 , and SO2OR 8 or two adjacent R 5 together with the aromatic group form a 5- to 8-membered saturated or unsaturated ring optionally containing one or two heteroatoms, and R 6 and R 6′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(en / ynyl), and Ar; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), Ar, and acyl; R 8 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, and -NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6-alkyl(alkenyl / alkynyl), provided that R 5 SO2OR 8 If R 8 Ga-NR 9 R 9′ Instead, R 5 SO2R 8 If R 8 is not a hydrogen atom, 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- provided that the compound is not 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.

[0228] In a further embodiment, R 1 and R 1 ' are independently hydrogen and C 1~6 - alkyl(alkenyl / alkynyl).

[0229] In a further embodiment, R 1 and R1 At least one of the ' is a hydrogen atom. In a further embodiment, s is 1.

[0230] In a further embodiment, s is 0.

[0231] In a further embodiment, R 2 is hydrogen, C 1~6 - selected from the group consisting of alkyl(en / ynyl), Ar, and halogen, with the proviso that when R is halogen, s is 0.

[0232] In a further embodiment, U is NR 2 ', and R and R 2 At least one of the ' is a hydrogen atom.

[0233] In a further embodiment, R 2 and R 2′ are hydrogen atoms.

[0234] In a further embodiment, X is CO.

[0235] In a further embodiment, q is 0.

[0236] In a further embodiment, q is 1.

[0237] In a further embodiment, Z is an oxygen atom.

[0238] In a further embodiment, R 3 is C 1~6 -Alkyl (alkenyl / alkynyl).

[0239] In further embodiments, each R 5 independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), Ar, cyano, halogen, halo-Cι ~6 -Alkyl (alkenyl / alkynyl), and C1~6 -alkyl(alkenyl / alkynyl)oxy, or two adjacent substituents together form a 5-8 membered saturated or unsaturated ring optionally containing 1 or 2 heteroatoms.

[0240] In a further embodiment, the Kv7 channel activator is {2-amino-4-[(4-tert-butylphenylamino)-methyl]-phenyl}-carbamic acid ethyl ester, (2-amino-4-phenylaminomethyl-phenyl)-carbamic acid ethyl ester, [2-amino-4-(aphthalen-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-isopropylphenyl {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-to N-{2-amino-4-[(3-fluorophenylamino)methyl]phenyl}-2,2-dimethylpropionamide, {4-[(4-chlorophenylamino)methyl]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)ethyl]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-methylphenyl}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-methylphenyl}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.

[0241] In a further embodiment, the Kv7 channel activator is a compound according to formula 11, wherein U is O, S, or C, s is O or 1, X is CO or SO, Z is O, S, or NR, and R 4However, hydrogen, Cι~6-alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cyclo(alkenyl), q is O or 1, and R 1 and R 1 ', but independently, hydrogen, C \ .6-Alkyl (alkenyl / alkynyl), C3 ~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-Cι ~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl), and halo-C 3~8 -cyclo(alkenyl), wherein R is selected from the group consisting of hydrogen, halogen, C 1-6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-Cι ~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1-6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), acyl, hydroxy-Cι -6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1-6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -cycloalkyl(alkenyl), and cyano, provided that R 2 is halogen or cyano, s is 0, s is 1, and U is NR 2 ', then R2 ', hydrogen, C 1-6 -Alkyl (alkenyl / alkynyl), C ~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-Cι ~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1-6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), acyl, hydroxy-..6-Alkyl(alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1-6 -Alkyl(alkenyl / alkynyl), and halo-C 3~8 -cycloalkyl(alkenyl), or R 2 and R 2 ' together form a 5-8 membered saturated or unsaturated ring optionally containing one further heteroatom, R 3 But C 1-6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-Cι -6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1-6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), hydroxy-Cι -6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -cycloalkyl(alkenyl), halo-Cj.6-alkyl(alkenyl / alkynyl), and halo-C 3~8 -cyclo(alkenyl), and Y is selected from the group according to the formula selected from the group consisting of: [ka] wherein the line represents a bond connecting the group represented by Y to the nitrogen atom, W is O or S, a is 0, 1, 2, or 3, b is 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 R 5 But independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), Ar, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-Cι ~6 -Alkyl (alkenyl / alkynyl), acyl, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halogen, halo-Cι ~6 -Alkyl (alkenyl / alkynyl), -CO-NR 6 R 6′ , cyano, nitro, -NR 7 R 7′ , -SR 8 , -SO2R 8 , and SO2OR 8 or two substituents together form a 5-8 membered saturated or unsaturated ring optionally containing one or two heteroatoms, and R 6 and R 6 ', but independently, hydrogen, C \ .6-Alkyl(alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(en / ynyl), and Ar; R 7 and R 7 ', but independently, hydrogen, C \ .6-Alkyl(alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6- selected from the group consisting of alkyl(en / ynyl), Ar, and acyl; R 8 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-Cι ~6 -Alkyl(alkenyl / alkynyl), Ar, and -NR 9 R 9 and R 9 and R 9 ' are independently hydrogen, C6-alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), provided that R 5 SO2OR 8 If R 8 NR 9 R 9’ Instead, R 5 SO2R 8 If R 8is not hydrogen, 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-tetrahydroxy-5,5,8,8-tetramethyl-2-naphthalenyl)amino]methylphenyl]-acetamide, N-[4-[[[3-(1H-imidazol-1-ylmethyl)phenyl]amino]methyl]phenyl]-acetamide, 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)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.

[0242] In a further embodiment, the Kv7 channel activator is a compound according to formula 11, wherein U is O, S, or NR 2 where s is O or 1, X is CO or SO2, Z is O, S, or NR, and R is hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~ s-Cycloalkyl(alkenyl)-Cι ~6 -Alkyl (alkenyl / alkynyl), hydroxy-Cι ~6 -Alkyl (alkenyl / alkynyl), and hydroxy-C 3~8 -cycloalk(en)yl, q is O or 1, and R and R are independently selected from the group consisting of hydrogen, C-alkyl(alken / ynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8-Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-Cι ~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -cycloalk(en)yl, halo-C1.6-alkyl(en / yn)yl, and halo-C3.8-cycloalk(en)yl, wherein R is selected from the group consisting of hydrogen, halogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-Cι ~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-Cι ~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-Cι ~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -cycloalkyl(alkenyl), and cyano, provided that R 2 is halogen or cyano, s is 0, s is 1, and U is NR 2 If R 2’ But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C ~8 -Cycloalkyl(alkenyl), C.8-Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C3.8-cycloalkyl (alkenyl), acyl, hydroxy-C^6-alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl), and halo-C 3~8-cycloalkyl(alkenyl), or R and R together form a 5-8 membered saturated or unsaturated ring optionally containing one further heteroatom, and R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -cycloalkyl(alkenyl), halo-Ci-6-alkyl(alkenyl / alkynyl), and halo-C 3- s-cycloalkyl(alkenyl), and Y is a group according to the formula selected from the group consisting of: [ka]

[0243] wherein the line represents a bond connecting the group represented by Y to the nitrogen atom; W is O or S; a is 0, 1, 2, or 3; h is 0, 1, 2, 3, or 4; c is 0 or 1; d is 0, 1, 2, or 3; e is 0, 1, or 2; f is O, 1, 2, 3, 4, or 5; 5 But independently, Cι ~6 -Alkyl(alkenyl / alkynyl), C3.8-Cycloalkyl(alkenyl), Ar, Cs-s-Cycloalkyl(alkenyl)-Ci-e-Alkyl(alkenyl / alkynyl), Ar-Cι ~6 -Alkyl (alkenyl / alkynyl), acyl, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), -CO-NR6 R 6’ , cyano, nitro, -NR 7 R 7 ', -SR 8 , -SO2R 8 , and SO2OR 8 or two substituents together form a 5-8 membered saturated or unsaturated ring optionally containing one or two heteroatoms, and R 6 and R 6 are independently hydrogen, C \ .6-Alkyl(alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(en / ynyl), and Ar; R 7 and R 7 ' are independently hydrogen, Cj.6-alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), Ar, and acyl; R 8 are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, and -NR 9 R 9 and R 9 and R 9 ' are independently hydrogen, Q.6-alkyl(alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-Cι ~6 -alkyl(alkenyl / alkynyl), provided that R 5 SO2OR 8 If R 8 Ga-NR 9 R9 ', not R 5 SO2R 8 If R s is not a hydrogen atom, or a salt thereof for increasing ion flux through potassium channels in a mammal, such as a human.

[0244] Formula 12 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 12. Such compounds are disclosed in International Publication No. WO2009015667A1, which corresponds to International Application No. PCT / DK2008 / 050191 published on February 5, 2009, and filed on July 31, 2008; International Application No. PCT / DK2004 / 000283, which corresponds to International Application No. PCT / DK2004 / 000283 published on November 11, 2004, and filed on April 23, 2004, which are incorporated herein by reference in their entireties. and U.S. Publication No. US20060264496A1, published November 23, 2006, which corresponds to U.S. Application No. 10 / 551,738, filed April 23, 2003, and U.S. Publication No. US20100256145A1, published October 7, 2010, which corresponds to U.S. Application No. 12 / 671,505, filed July 31, 2008. In the event of any discrepancy in terminology relating to Formula 12, these references, which are incorporated herein by reference, control.

[0245] In embodiments, the Kv7 channel activator is a compound according to Formula 12: [ka] where the dotted line represents an optional bond and R 1 and R 1′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6-Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 1 and R 1′ together with the carbon atoms to which they are attached form a 3- to 8-membered saturated or unsaturated ring optionally containing 1 or 2 heteroatoms, s is 0 or 1, and U is O, NR 11 , S, SO2, SO2NR 11 , CO-O, or CO-NR 11 and R 11 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 2 and R 2′ together with the nitrogen atom to which they are attached form a 4- to 8-membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, and R 2 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -NO2, NR 10 R 10′-C 1~6 Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 3~8 -cycloalkyl(alkenyl), and NR 10 R 10′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 10 and R 10′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), hydroxy-Cl -6-Alkyl(alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 10 and R 10′ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 2 is NO2, halogen, or cyano, s is 0, and R 2 , R 2 is a hydrogen atom or acyl, and s is 1, U is NR 11 , O, or S, and the group -(U) s- R 2 is linked to the 4- or 6-position of the indole or indoline, q is 0 or 1, Z is O or S, and X is CO or SO, provided that when q is 0, X is SO; R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), heterocycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), C1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -cycloalkyl(alkenyl), Ar-heterocycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-heterocycloalkyl(alkenyl), Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C3~8 -Cycloalkyl(alkenyl), hydroxy-heterocycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-heterocycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-Ar, Halo-C 3~8 -Cycloalkyl(alkenyl)-Ar, halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)-Ar, Halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl)-Ar, Cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-heterocycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), cyano-C 1~6-Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), acyl-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 3~8 -Cycloalkyl(alkenyl), acyl-heterocycloalkyl(alkenyl), acyl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), -NR 12 R 12′ , optionally substituted NR 12 R 12′- C 1~6 -Alkyl(alkenyl / alkynyl), optionally substituted NR 12 R 12′- C 3~8 -cyclo(alkenyl) and optionally substituted NR 12 R 12′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 12 and R 12’ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C3 ~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8-Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 12 and R 12’ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 3 NR 12 R 12′ and Y represents a radical of the formula from the group: [ka] wherein the line represents a bond connecting the group represented by Y to a carbon atom, W is O or S, T is N, NE, or O, L is N, C, or CH, a is 0, 1, 2, or 3, b is 0, 1, 2, 3, or 4, c is 0 or 1, d is 0, 1, 2, or 3, e is 0, 1, or 2, f is 0, 1, 2, 3, 4, or 5, g is 0, 1, 2, 3, or 4, h is 0, 1, 2, or 3, and j is 0, 1, 2, or 3, with the proviso that when T is a nitrogen atom, j is 0, 1, 2, or 3, and when T is an NH or oxygen atom, j is 0, 1, or 2; k is 0, 1, 2, 3, or 4; 5 But independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8-Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-thio, Ar-oxy, acyl, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3-8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -CO-NR 6 R 6′ , cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3-8 -Cycloalkyl(alkenyl), cyano-C 3-8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -NR 7 R 7′ , -SR 8 , and -SO2R 8 or two adjacent R 5 the substituents, together with the aromatic group to which they are attached, form a 4- to 8-membered ring, optionally containing one or two heteroatoms, and R 6 and R 6’ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(en / ynyl), and Ar; R 7 and R 7′ are independently hydrogen, C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), Ar, and acyl; R 8 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, and -NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), provided that R 8 Ga-NR 9 R 9′ If R 5 Ga-SR 8 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 a salt thereof.

[0246] In a further embodiment, R 1 or R 1The least common one is the hydrogen atom.

[0247] In a further embodiment, R 1 and R 1’ is a hydrogen atom.

[0248] In a further embodiment, s is 0.

[0249] In a further embodiment, s is 1.

[0250] In a further embodiment, R 2 is a hydrogen atom.

[0251] In a further embodiment, R 2 is NO2 or a halogen atom.

[0252] In a further embodiment, U is NR 11 is.

[0253] In a further embodiment, R 11 is a hydrogen atom.

[0254] In a further embodiment, X is CO.

[0255] In a further embodiment, X is SO2.

[0256] In a further embodiment, q is 0.

[0257] In a further embodiment, q is 1.

[0258] In a further embodiment, Z is an oxygen atom.

[0259] In a further embodiment, R 3 is C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-oxy-C 1~6-Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl(alkenyl / alkynyl), and -NR 12 R 12′ wherein R 3 NR 12 R 12′ If , then q is 0.

[0260] In a further embodiment, R 3 is NR 12 R 12′ where q is 0 and R 12 and R 12′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), Ar, and Ar-C 1~6 -alkyl(alkenyl / alkynyl) or R 12 and R 12′ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring, optionally containing 1, 2, or 3 additional heteroatoms.

[0261] In further embodiments, each R 5 are independently hydrogen, C 1~6 -Alkyl(alkenyl / alkynyl), Ar, Ar-thio, Ar-oxy, halogen, and halo-C 1~6 - alkyl (alkenyl / alkynyl), or two adjacent R 5 together with the aromatic group to which they are attached form a 4- to 8-membered ring, optionally containing one or two heteroatoms.

[0262] In a further embodiment, the Kv7 channel activator is 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-thiophen-2-ylacetamide 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]- Amides, [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-chloro thiophen-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-( 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-ethylurea, 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-phenethylurea, 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]-3-phenethylurea Hydro-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]-aceto Amide, 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-trifluoromethylbenzamide] 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]-2,2-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-chlorophenylsulfanyl)-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]-butyl Amide, 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 N-(1-benzo[b]thiophen-2-ylmethyl-2,3-dihydro-1H-indol-5-yl)-butyramide, 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-methylthiophen-2-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, 4-(4-Fluorophenyl)-N-[1-(4-isopropylbenzyl)-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, 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-(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 -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-yl]- 2-(4-fluorophenyl)-N-[1-(4-pyrrol-1-yl-benzyl)-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.

[0263] formula 13 In embodiments, 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, which corresponds to International Application No. PCT / DK2008 / 050191, published February 5, 2009, filed July 31, 2008, and U.S. Publication No. US20100256145A1, which corresponds to U.S. Application No. 12 / 671,505, filed July 31, 2008, which are incorporated herein by reference in their entireties. In the event of any discrepancy in terminology relating to Formula 13, the references incorporated herein by reference shall control.

[0264] In embodiments, the Kv7 channel activator is a compound according to Formula 13: [ka] In the formula, q is 0 or 1, W is O or S, X is CO, Z is O, and R1 is halogen, cyano, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -cycloalkyl(alkenyl)oxy, and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alk(en / yn)oxy, wherein R2 is selected from the group consisting of halogen, cyano, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alk(en / yn)yloxy, optionally substituted phenyl, and optionally substituted pyridyl, wherein phenyl and pyridyl are independently selected from the group consisting of halogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), or C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - optionally substituted with one or more substituents which are alkyl(en / ynyl), and R3 is C 1~10 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), and Ar, and each of R4, R5, R6, and R7 is independently selected from the group consisting of hydrogen and Ar, or a salt thereof, as the free base.

[0265] In a further embodiment, the Kv7 channel activator is N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-2-(4-fluoro-phenyl)-acetamide as the free base, 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)-propionamide, N-(2-bromo-4-morpholin-4-yl-6-trifluoromethyl-phenyl)- 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 1-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 Propyl-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-mo Hexanoic acid (2-methyl-4-morpholin-4-yl-6-trifluoromethyl-phenyl)-acetamide, 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, or a pharmaceutically acceptable salt thereof.

[0266] formula 14 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 14. Such compounds are disclosed in International Publication No. WO2009015667A1, which corresponds to International Application No. PCT / DK2008 / 050191, published February 5, 2008, filed July 31, 2008, and International Application No. PCT / DK2005 / 000560, published March 23, 2006, filed September 2, 2005, which are incorporated herein by reference in their entireties. No. 7,601,870, published October 13, 2009, corresponding to U.S. application Ser. No. 11 / 312,664, filed December 20, 2005, and U.S. application Ser. No. US20100256145A1, published October 7, 2010, corresponding to U.S. application Ser. No. 12 / 671,505, filed July 31, 2008. In the event of any discrepancy in terminology relating to Formula 14, these references, incorporated herein by reference, shall control.

[0267] In embodiments, the Kv7 channel activator is a compound according to Formula 14: [ka] wherein Z is O or S, q is 0 or 1, and R 1 and R 2 each independently represents a halogen, a cyano, an amino, a C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -heterocycloalkyl(alkenyl), aryl, heteroaryl, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -heterocycloalkenyl(alkyl)oxy, C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, and C 3~8 -heterocycloalkenyloxy; R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8-heterocycloalkenyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C alkyl(alkenyl / alkynyl), heteroaryl-C 3~8 -Cycloalkyl(alkenyl), heteroaryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), amino-C 1~6 -Alkyl (alkenyl / alkynyl), amino-C 3~8 -Cycloalkyl(alkenyl), amino-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 4 But halogen, cyano, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8-Heterocycloalkyl(alkenyl), aryl, heteroaryl, aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 5 R 6 , and R 7 NH-C 1~6 - alkyl (alkenyl / alkynyl), R 5 and R 6 are independently hydrogen, aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C 3~8 -cycloalkyl(alkenyl), and heteroaryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6-alkyl(alkenyl / alkynyl), provided that R 5 and R 6 is not simultaneously hydrogen, and R 7 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -cycloalkyl(alkenyl), and heteroaryl, or a pharmaceutically acceptable salt thereof.

[0268] In a further embodiment, the Kv7 channel activator is 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)- 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 methyl-4-(4-trifluoromethyl-benzylamino)-2,6-dimethyl-phenyl)-carbamic acid propyl ester, {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 {2,6-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 N-[4-(4-chlorophenylamino)methyl]-2,6-dimethylphenyl]-amide, Pentanoic acid (4-[(4-chlorophenylamino)-methyl]-2,6-dimethylphenyl)-amide, 2-(4-chlorophenyl)-N-[4-(4-chlorophenylamino)-methyl]-2,6-dimethylphenyl)-acetamide, {2,6-dimethyl-4-[(4-trifluoromethylphenylamino)-methyl]-phenyl}-carbamic acid 2-methoxyethyl ester, N-{4-[(5-chloro-pyridin-2-ylamino)-methyl]-2,6-dimethylphenyl}-2-cyclopentylacetamide, 2-cyclopentylacetamide, Clopentyl-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.

[0269] In a further embodiment, Z is O or S, q is 0, and R 1 and R 2 are each independently halogen, cyano, amino, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -cycloalkyl(alkenyl)oxy, and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl)oxy; R 3 is C 1~8 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), amino-C 1~6 -Alkyl (alkenyl / alkynyl), amino-C 3~8 -Cycloalkyl(alkenyl), amino-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 4 is halogen, cyano, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 5 R 6 , and R 7 NH-C 1~6 - alkyl(alkenyl / alkynyl), R 5 and R 6 are each independently hydrogen, aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 alkyl(alkenyl / alkynyl), provided that R 5 and R 6 and R cannot both be hydrogen. 7 is C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), and aryl-C 3~8 -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.

[0270] In a further embodiment, R 1 and R 2 are each independently a halogen, an amino, or C 1~6 -Alkyl(alkenyl / alkynyl), aryl, and halo-C 1~6 - alkyl(alkenyl / alkynyl).

[0271] In a further embodiment, R 3 is C 1~8 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), and amino-C 1~6 - alkyl(alkenyl / alkynyl).

[0272] In a further embodiment, R 4 is a halogen, C 1~6 -Alkyl (alkenyl / alkynyl), NR 5 R 6 , and R 7 NH-C 1~6 - alkyl(alkenyl / alkynyl), R 5 , R 6 , and R 7 is as previously defined.

[0273] In a further embodiment, R 4 is NR 5 R 6 where R 5 and R 6 are independently hydrogen, aryl-C 1~6 -Alkyl (alkenyl / alkynyl), and C 1~6 -alkyl(alkenyl / alkynyl), provided that R 5 and R 6 cannot both be hydrogen.

[0274] In a further embodiment, R 4 is R 7 NH-C 1~6 -alkyl(alkenyl / alkynyl), where R 7 is aryl.

[0275] In further embodiments, any aryl is independently selected from amino, halogen, cyano, C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy, C 1~6-Alkyl(alkenyl / alkynyl)oxy, halo-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, di-(C 1~6 -Alkyl(alkenyl / alkynyl)amino, C 1~6 -Alkyl(alkenyl / alkynyl)-CO-NH-, and C 1~6 -alkyl(alkenyl / alkynyl)-sulfonamide, or two adjacent substituents together with the aryl groups to which they are attached are optionally substituted with one or more C 1~6 - may form a 4- to 8-membered ring optionally substituted with alkyl(alkenyl / alkynyl) groups.

[0276] In a further embodiment, the Kv7 channel activator is a compound according to formula 14, wherein Z is O or S, q is 0, and R 1 and R 2 each independently represents halogen, cyano, amino, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -cycloalkyl(alkenyl)oxy, and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl)oxy; R 3 But C 1~8 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), amino-C 1~6 -Alkyl (alkenyl / alkynyl), amino-C 3~8 -Cycloalkyl(alkenyl), amino-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 4 But halogen, cyano, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8-Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 5 R 6 , and R 7 NH-C 1~6 - alkyl(alkenyl / alkynyl), R 5 and R 6 each independently represents hydrogen, aryl-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 3~8 -Cycloalkyl(alkenyl), aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), provided that R 5 and R 6 and R cannot both be hydrogen. 7 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), aryl-C 1~6 -Alkyl (alkenyl / alkynyl), and aryl-C 3~8-cycloalk(en)yl, or a pharmaceutically acceptable salt thereof, with the proviso that the compound of formula I is not N-(4-bromo-2,6-dimethyl-phenyl)-2-cyclopentyl-acetamide, and a pharmaceutically acceptable carrier or diluent.

[0277] formula 15 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 15. Such compounds are disclosed in International Publication No. WO2009015667A1, which corresponds to International Application No. PCT / DK2008 / 050191 published on February 5, 2009, and filed on July 31, 2008; International Application No. PCT / DK2006 / 000123, which corresponds to International Application No. PCT / DK2006 / 000123 published on September 8, 2006, and filed on March 2, 2006, which are incorporated herein by reference in their entireties. Publication No. WO2006092143A1, U.S. Patent No. 7,812,020, published October 12, 2010, corresponding to U.S. Application No. 11 / 817,340, filed March 2, 2006, and U.S. Publication No. US20100256145A1, published October 7, 2010, corresponding to U.S. Application No. 12 / 671,505, filed July 31, 2008. In the event of any discrepancy in terminology relating to Formula 15, these references, which are incorporated herein by reference, control.

[0278] In embodiments, the Kv7 channel activator is a compound according to Formula 15: [ka] In the formula, q is 0 or 1, and R 1 and R 2 each independently represents a halogen, a cyano, a C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6-Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -cycloalkyl(alkenyl)oxy, and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl)oxy; R 3 But C 1~8 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), optionally substituted aryl-C 1~6 -alkyl(alkenyl / alkynyl), optionally substituted aryl-C 3~8 -cycloalkyl(alkenyl), optionally substituted aryl-C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C 3~8 -Cycloalkyl(alkenyl), heteroaryl-C 3~8 -Cycloalkyl(alkenyl)-C1~6 -Alkyl (alkenyl / alkynyl), NR 4 R 5- C 1~6 -Alkyl (alkenyl / alkynyl), NR 4 R 5- C 3~8 -cycloalkyl(alkenyl), NR 4 R 5- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 4 and R 5 each independently being hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), as the free base, or a pharmaceutically acceptable salt thereof.

[0279] In a further embodiment, the Kv7 channel activator is (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-dichloro-phenyl)-( ... Methyl-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 Cetamide, 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 onamide, 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-pi 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)-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.

[0280] In a further embodiment, q is 0 or 1 and R 1 and R 2 are each independently a halogen, a cyano, or a C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -cycloalkyl(alkenyl)oxy, and C 3~8-Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl)oxy; R 3 is C 1~8 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), optionally substituted aryl-C 1~6 -alkyl(alkenyl / alkynyl), optionally substituted aryl-C 3~8 -cycloalkyl(alkenyl), optionally substituted aryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -heterocycloalkenyl-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C 1~6 -Alkyl(alkenyl / alkynyl), heteroaryl-C 3~8 -Cycloalkyl(alkenyl), heteroaryl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), NR 4 R 5- C 1~6 -Alkyl (alkenyl / alkynyl), NR 4 R 5- C 3~8 -cycloalkyl(alkenyl), NR 4 R 5- C 3~8 -Cycloalkyl(alkenyl)-C 1~6-Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 4 and R 5 are each independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl).

[0281] formula 16 In embodiments, 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, which corresponds to International Application No. PCT / DK2008 / 050191, published February 5, 2009, filed July 31, 2008, and U.S. Publication No. US20100256145A1, which corresponds to U.S. Application No. 12 / 671,505, filed July 31, 2008, which are incorporated herein by reference in their entireties. In the event of any discrepancy in terminology relating to Formula 16, the references incorporated herein by reference shall control.

[0282] In embodiments, the Kv7 channel activator is a compound according to Formula 16: [ka] In the formula, q is 0 or 1, and R 1 and R 2 are independently hydrogen and optionally substituted aryl-C 1~6 -alkyl(alkenyl / alkynyl), provided that R 1 and R 2 are not both hydrogen, or R 1 and R 2 together with the nitrogen to which they are attached form a 5- to 7-membered ring optionally containing further heteroatoms, and R 2 and R 4 are independently hydrogen, halogen, cyano, amino, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halo-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halo-C 3~8 -Cycloalkyl(alkenyl)oxy and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl)oxy, with the proviso that R 3 and R 4 are not both hydrogen, and R 5 But C 1~10 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6-alkyl(alkenyl / alkynyl), optionally substituted aryl-C 1~6 - a compound selected from the group consisting of alkyl(en / alkynyl), and optionally substituted aryl, as the free base, or a pharmaceutically acceptable salt thereof.

[0283] In a further embodiment, the Kv7 channel activator is N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-cyclopentylacetamide as the free base, 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 amide, 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, or a pharmaceutically acceptable salt thereof.

[0284] formula 17 In embodiments, 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 herein by reference in its entirety. In the event of any discrepancy in terminology relating to Formula 17, this reference, incorporated herein by reference, will control.

[0285] In embodiments, the Kv7 channel activator is a compound according to Formula 17: [ka] In the formula, q is 0 or 1, and R 1 and R 2 are independently hydrogen and optionally substituted aryl-C 1~6 -alkyl(alkenyl / alkynyl), provided that R 1 and R 2 are not both hydrogen, or R 1 and R 2 together with the nitrogen to which they are attached form a 5- to 7-membered ring optionally containing further heteroatoms, and R 3 and R 4 are independently hydrogen, halogen, cyano, amino, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halo-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halo-C 3~8-Cycloalkyl(alkenyl)oxy and halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl)oxy, with the proviso that R 3 and R 4 are not both hydrogen, and R 5 But C 1~10 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), optionally substituted aryl-C 1~6 - a compound selected from the group consisting of alkyl(en / alkynyl), and optionally substituted aryl, as the free base, or a pharmaceutically acceptable salt thereof.

[0286] In a further embodiment, q is 0.

[0287] In a further embodiment, q is 1.

[0288] In a further embodiment, R 1 and R 2 are independently hydrogen and optionally substituted aryl-C 1~6 - alkyl(alkenyl / alkynyl), provided that R 1 and R 2 are not both hydrogen.

[0289] In a further embodiment, R 1 and R 2 together with the nitrogen atom to which they are attached form a 5- to 7-membered ring optionally containing additional heteroatoms.

[0290] In a further embodiment, the additional heteroatom is oxygen.

[0291] In a further embodiment, the ring is a six-membered ring.

[0292] In a further embodiment, the ring is a morpholine ring.

[0293] In a further embodiment, R 3 and R 4 are independently amino and C 1~6 - alkyl(en / ynyl), preferably methyl.

[0294] In a further embodiment, R 5 is C 1~10 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), optionally substituted aryl-C 1~6 -selected from the group consisting of alkyl(alkenyl / alkynyl), and optionally substituted aryl

[0295] In a further embodiment, the Kv7 channel activator is N-[4-amino-6-methyl-2-(4-trifluoromethylbenzylamino)-pyrimidin-5-yl]-2-cyclopentylacetamide as the free base, 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, or a salt thereof.

[0296] formula 18 In embodiments, 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, corresponding to International Application No. PCT / DK2004 / 000283, filed April 23, 2004, and U.S. Publication No. US20060264496A1, published November 23, 2006, corresponding to U.S. Application No. 10 / 551,783, filed April 23, 2004, which are incorporated herein by reference in their entireties. In the event of any discrepancy in terminology relating to Formula 18, these references, incorporated herein by reference, shall control.

[0297] In embodiments, the Kv7 channel activator is a compound according to Formula 18: [ka] where the dotted line represents an optional bond and R 1 and R 1′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8-Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 1 and R 1′ together with the carbon atoms to which they are attached form a 3- to 8-membered saturated or unsaturated ring optionally containing 1 or 2 heteroatoms, s is 0 or 1, and U is O, NR 11 , S, SO2, SO2NR 11 , CO-O, or CO-NR 11 and R 11 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 2 and R 11 together with the nitrogen atom to which they are attached form a 4- to 8-membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, and R 2 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl, hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8-Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -NO2, NR 10 R 10′- C 1~6 -Alkyl (alkenyl / alkynyl), NR 10 R 10′- C 3~8 -cycloalkyl(alkenyl), and NR 10 R 10′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 10 and R 10′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8-Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl) or R 10 and R 10′ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 2 is NO2, halogen, or cyano, provided that s is 0; 2 is a hydrogen atom or acyl, and s is 1, then U is NR 11 , O, or S, and the group -(U) s- R 2 is linked to the 4- or 6-position of the indole or indoline, q is 0 or 1, Z is O or S, and X is CO or SO, with the proviso that when X is SO, q is 0; R 3 But C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), heterocycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -cycloalkyl(alkenyl), Ar-heterocycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), C 1~6-Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 3~8 -Cycloalkyl(alkenyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-heterocycloalkyl(alkenyl), Ar-oxy-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-C 1~6 -Alkyl (alkenyl / alkynyl), C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy-carbonyl-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-heterocycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-heterocycloalkyl(alkenyl), halo-C3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), halo-C 1~6 -Alkyl(alkenyl / alkynyl)-Ar, Halo-C 3~8 -Cycloalkyl(alkenyl)-Ar, halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)-Ar, Halo-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl)-Ar, Cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), cyano-heterocycloalkyl(alkenyl), cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), cyano-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 3~8 -Cycloalkyl(alkenyl), acyl-heterocycloalkyl(alkenyl), acyl-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-C 3~8 -Cycloalkyl(alkenyl), acyl-C 1~6 -Alkyl(alkenyl / alkynyl)-heterocycloalkyl(alkenyl), and -NR 12 R 12′, optionally substituted NR 12 R 12′- C 1~6 -Alkyl(alkenyl / alkynyl), optionally substituted NR 12 R 12′- C 3~8 -cycloalkyl(alkenyl), optionally substituted NR 12 R 12′- C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(alkenyl / alkynyl), R 12 and R 12′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-C 3~8 -Cycloalkyl(alkenyl), Ar-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 1~6 -Alkyl (alkenyl / alkynyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl), hydroxy-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3~8 -Cycloalkyl(alkenyl), and cyano-C 3~8 -Cycloalkyl(alkenyl)-C 1~6-alkyl(alkenyl / alkynyl) or R 12 and R 12′ together with the nitrogen atom to which they are attached form a 4-8 membered saturated or unsaturated ring optionally containing 1, 2, or 3 additional heteroatoms, with the proviso that R 3 NR 12 R 12′ provided that q is 0, then Y is a group according to the formula: [ka] 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, and j is 0, 1, 2, or 3, with the proviso that when T is a nitrogen atom, j is 0, 1, 2, or 3, and when T is an NH or oxygen atom, j is 0, 1, or 2; k is 0, 1, 2, 3, or 4; 5 But independently, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), Ar, Ar-C 1~6 -Alkyl (alkenyl / alkynyl), Ar-thio, Ar-oxy, acyl, C 1~6 -Alkyl(alkenyl / alkynyl)oxy, C 3~8 -Cycloalkyl(alkenyl)oxy, C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl)oxy, halogen, halo-C 1~6 -Alkyl (alkenyl / alkynyl), halo-C 3~8 -Cycloalkyl(alkenyl), halo-C 3-8-Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -CO-NR 6 R 6′ , cyano, cyano-C 1~6 -Alkyl (alkenyl / alkynyl), cyano-C 3-8 -Cycloalkyl(alkenyl), cyano-C 3-8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl (alkenyl / alkynyl), -NR 7 R 7′ , -SR 8 , and -SO2R 8 or two adjacent R 5 together with the aromatic group to which they are attached form a 4- to 8-membered ring, optionally containing 1 or 2 heteroatoms, and R 6 and R 6′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - alkyl(en / ynyl), and Ar; R 7 and R 7′ are independently hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 - selected from the group consisting of alkyl(en / ynyl), Ar, and acyl; R 8 But hydrogen, C 1~6 -Alkyl (alkenyl / alkynyl), C 3~8 -Cycloalkyl(alkenyl), C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -Alkyl(alkenyl / alkynyl), Ar, and -NR 9 R 9′ and R 9 and R 9′ are independently hydrogen, C 1~6-Alkyl (alkenyl / alkynyl), C 3~8 -cycloalkyl(alkenyl), and C 3~8 -Cycloalkyl(alkenyl)-C 1~6 -alkyl(alkenyl / alkynyl), provided that R 8 Ga-NR 9 R 9′ If R 5 Ga-SR 8 or a salt thereof, provided that it is not

[0298] formula 19 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 19. Such compounds are described in U.S. Patent No. 9,248,122, issued February 2, 2016, and corresponding to U.S. Application No. 14 / 091,395, filed November 27, 2013, which is incorporated herein by reference in its entirety. In the event of any discrepancy in terminology relating to Formula 19, this reference, incorporated herein by reference, will control.

[0299] In embodiments, the Kv7 channel activator is a compound according to Formula 19: [ka] In the formula, A 1 , A 2 , and A 3 However, independently of each other, CR 4 , N, O, S, or N(CH3), and A 4 But, CR 4 or N, n represents 0 or 1, provided that A 1 , A 2 , A 3 , and A 4 At least one of the 4 If n is 0, then A 1 , A 2 , and A 3 represents O, S, or N(CH3), or n represents 1; then A 1 , A2 , and A 3 However, independently of each other, CR 4 or N, R 1 is unsubstituted or mono- or polysubstituted C 1~10 - an aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~8 - optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, C 3~10 - an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~8 - represents aryl or heteroaryl, optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, and R 2 , F, Cl, Br, I, CN, CF3, C(=O)H, NO2, OCF3, SCF3, C 1~4 -Aliphatic residue, C(=O)-C 1~4 -Aliphatic residue, C(=O)-C 1~4 -Aliphatic residue, C(=O)-NH-C 1~4 -Aliphatic residue, C(=O)-N(C 1~4 -aliphatic residue)2, OC 1~4 -Aliphatic residue, OC(=O)-C 1~4 -Aliphatic residue, SC 1~4 -Aliphatic residue, S(=O) 2- C 1~4 -Aliphatic residue, S(=O) 2- O.C. 1~4 -Aliphatic residue (C 1~4 - the aliphatic residue may in each case be unsubstituted or mono- or polysubstituted), in each case unsubstituted or mono- or polysubstituted, in each case C 1~4 - optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, and R 3 is unsubstituted or mono- or polysubstituted C 2~10 - an aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~8- optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, C 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, or SR 5 , OR 6 , or N(R 7 R 8 ) and R 5 and R 6 In either case, unsubstituted or mono- or polysubstituted C 1~10 - an aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~8 - optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, C 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, provided that R 5 or R 6 represents a 3- to 10-membered heterocyclic aliphatic residue, provided that the 3- to 10-membered heterocyclic aliphatic residue is linked via a carbon atom, 7 is unsubstituted or mono- or polysubstituted C 1~10 - an aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~8 - optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, C 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, provided that R 7 represents a 3- to 10-membered heterocyclic aliphatic residue, provided that the 3- to 10-membered heterocyclic aliphatic residue is linked via a carbon atom, 8 is unsubstituted or mono- or polysubstituted C 1~10 - represents an aliphatic residue, or R 7 and R 8 together with the nitrogen atom connecting them form a 3- to 10-membered heterocyclic aliphatic residue, and each R 4 are independently H, F, Cl, Br, I, CN, CF3, CHF2, CH2F, OCF3, OCHF2, OCH2F, SCF3, OC 1~4 -Aliphatic residue, C 1~4 -Aliphatic residue, or S(=O) 2- C1~4 - represents an aliphatic residue, wherein "aliphatic group" and "aliphatic residue" may in each case be branched or unbranched, saturated or unsaturated, "alicyclic residue" and "heterocyclic aliphatic residue" may in each case be saturated or unsaturated, and "mono- or poly-substitution" with respect to "aliphatic group", "aliphatic residue", "alicyclic residue", and "heterocyclic aliphatic residue" refers to F, Cl, Br, I, NO, NH, NH(C) with respect to the corresponding residue or group. 1~4 -aliphatic residue), N(C 1~4 -aliphatic residue)2, NH-C(=O)-C 1~4 Aliphatic residue, N(C 1~4 aliphatic residue)-C(=O)-C 1~4 Aliphatic residue, NH-S(=O) 2- C 1~4 Aliphatic residue, N(C 1~4 aliphatic residue)-S(=O) 2- C 1~4 -Aliphatic residues, =O, OH, OCF3, OC 1~4 -Aliphatic residue, OC(=O)-C 1~4 -Aliphatic residues, SH, SCF3, SC 1~4 -Aliphatic residue, S(=O)2OH, S(=O) 2- C 1~4 -Aliphatic residue, S(=O) 2- OC 1~4 -Aliphatic residue, S(=O) 2- NH(C 1~4 -aliphatic residue), S(=O) 2- N(C 1~4 -Aliphatic residues)2, CN, CF3, CHO, COOH, C 1~4 -Aliphatic residue, C(=O)-C 1~4 -Aliphatic residue, C(=O)-OC 1~4 -Aliphatic residue, C 3~6 -Alicyclic residue, 3-7 membered heterocyclic aliphatic residue, C(=O)NH2, C(=O)-NH(C 1~4 -aliphatic residues), and C(=O)-N(C 1~4-aliphatic residues)2, and "mono- or polysubstitution" with respect to "aryl" and "heteroaryl" refers to the replacement of one or more hydrogen atoms, each independently of the other, by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, [ka] NH(C 1~4 -aliphatic residue), N(C 1~4 -aliphatic residue)2, NH-C(=O)-C 1~4 -Aliphatic residue, N(C 1~4 aliphatic residue)-C(=O)-C 1~4 -Aliphatic residue, NH-S(=O) 2- C 1~4 -Aliphatic residue, N(C 1~4 -Aliphatic residue)-S(=O) 2- C 1~4 -Aliphatic residues, OH, OCF3, OC 1~4 -Aliphatic residue, OC(=O)-C 1~4 -Aliphatic residues, SH, SCF3, SC 1~4 -Aliphatic residue, S(=O)2OH, S(=O) 2- C 1~4 -Aliphatic residue, S(=O) 2- OC 1~4 -Aliphatic residue, S(=O) 2- NH(C 1~4 -aliphatic residue), S(=O) 2- N(C 1~4 -Aliphatic residue)2, CN, CF3, C(=O)H, C(=O)OH, C 1~4 -Aliphatic residue, C(=O)-C 1~4 -Aliphatic residue, C(=O)-OC 1~4 -Aliphatic residue, C 3~6 -alicyclic residues, 3-7 membered heterocyclic aliphatic residues, benzyl, aryl, heteroaryl, C(=O)NH2, C(=O)-NH(C 1~4 -aliphatic residues), and C(=O)-N(C 1~4-aliphatic residues)2, in the form of individual single stereoisomers or mixtures of stereoisomers in any ratio and / or in the form of free compounds, solvates and / or physiologically acceptable salts.

[0300] In a further embodiment, A 1 , A 2 , and A 3 are independent of each other, CR 4 , N, O, S, or N(CH3), and A 4 is CR 4 or N, n represents 0 or 1, provided that A 1 , A 2 , A 3 , and A 4 At least one of the 4 If n is 0, then A 1 , A 2 , and A 3 represents O, S, or N(CH3), or n represents 1; 1 , A 2 , and A 3 However, independently of each other, CR 4 or N, R 1 is unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -aliphatic residues, and C(=O)OH(C 1~4 Aliphatic residues are unsubstituted or include F, Cl, Br, I, OH, OCF3, CF3, and OC 1~4 -aliphatic residues), C 1~10- represents an aliphatic residue, or in each case unsubstituted or F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residue, C(=O)-OH, C 3~8 -alicyclic residues and 3- to 7-membered heterocyclic aliphatic residues (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - aliphatic residues, C 3~8 - the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH (which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH), 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue (C 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue is C 1~8 - optionally linked via an aliphatic group, which is then in each case unsubstituted or substituted with F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4- aliphatic residues, and C(=O)OH), or in each case unsubstituted or with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residues)2, OH, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residues, C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, O 3~8 -alicyclic residue, 3- to 7-membered heterocyclic aliphatic residue, [ka] represents an aryl or heteroaryl mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl, and oxazolyl; C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, which in each case may be unsubstituted or may be selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residues)2, OH, OC 1~4 -Aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5; 3~6- the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues and C(=O)OH, and the aryl or heteroaryl residue may in each case be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH. 1~8 - optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 - aliphatic residues, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of CF3, CN, and C(=O)OH, R 2 is F, Cl, Br, I, CN, CF3, NO2, OCF3, SCF3, C 1~4 -Aliphatic residue, SC 1~4 -Aliphatic residue, OC 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - which may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, or In each case, it is unsubstituted or mono- or polysubstituted, and in each case, C 1~4 -Optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4- an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of CF3, CN, and C(=O)OH; 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, and R 3 is unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -aliphatic residues, and C(=O)OH(C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 2~10 - represents an alicyclic residue, or or In each case, it may be unsubstituted or may be substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -aliphatic residues, and C(=O)OH(C 1~4 The aliphatic residues are unsubstituted or include F, Cl, Br, I, OH, OCF3, CF3, and OC 1~4 -aliphatic residues), C 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue (C 3~10 -The alicyclic residue or the 3- to 10-membered heterocyclic aliphatic residue is, in either case, C 1~8- optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH, or or SR 5 , OR 6 , or N(R 7 R 8 ), wherein R 5 and R 6 is in each case unsubstituted or is substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -aliphatic residues, and C(=O)OH(C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 1~10 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residue, C(=O)-OH, C 3~8 -alicyclic residues and 3- to 7-membered heterocyclic aliphatic residues (C1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - aliphatic residues, C 3~8 - the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH (which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH), 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, C 3~10 -The alicyclic residue or the 3- to 10-membered heterocyclic aliphatic residue is, in either case, C 1~8 - optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH, provided that R 5 or R 6 represents a 3- to 10-membered heterocyclic aliphatic residue, provided that the 3- to 10-membered heterocyclic aliphatic residue is linked via a carbon atom, 7 is unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residue, C(=O)-OC 1~4 -aliphatic residues, and C(=O)OH(C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and unsubstituted OC 1~4 -aliphatic residues), C 1~10 - represents an alicyclic residue, or in each case unsubstituted or substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residue, C(=O)OH, C(=O)-OC 1~4 -Aliphatic residue, C 3-6 -alicyclic residues and 3- to 7-membered heterocyclic aliphatic residues (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - aliphatic residues, C 3~6 - the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH (which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH), 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, C3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue is O 1~0 - optionally linked via an aliphatic group, which is then in each case unsubstituted or substituted with F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residue, C(=O)-OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH, provided that R 7 represents a 3- to 10-membered heterocyclic aliphatic residue, provided that the 3- to 10-membered heterocyclic aliphatic residue is linked via a carbon atom; and / or R 8 is unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -aliphatic residues, and C(=O)OH(C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 1~10 - represents an aliphatic residue, or or R 7 and R 8 together with the nitrogen atom connecting them are unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4-Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residues, and C(=O)OH, C 3~6 - a 3- to 10-membered heterocyclic aliphatic residue mono- or polysubstituted with at least one substituent selected from the group consisting of an alicyclic residue and a 3- to 7-membered heterocyclic aliphatic residue, 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, and / or C 3~6 - the alicyclic residue or the 3- to 7-membered heterocyclic aliphatic residue is in each case unsubstituted or is substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH, R 7 and R 8 The 3- to 10-membered heterocyclic aliphatic residues formed together with the nitrogen atom connecting them by the formula (I) can be optionally fused with an aryl or heteroaryl, and the aryl or heteroaryl residues thus fused, for their part, can be unsubstituted or can be substituted with F, Cl, Br, I, NO, NH, NH(C), respectively. 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residues)2, OH, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residues, C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5, C 3~6 -alicyclic residue, 3- to 7-membered heterocyclic aliphatic residue, [ka] may be mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl, and oxazolyl; C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, which in each case may be unsubstituted or may be selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residues)2, OH, OC 1~4 -Aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5; 3~6 The alicyclic residue or the 3- to 7-membered heterocyclic aliphatic residue may in each case be unsubstituted or may be substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)-OH, and each R 4 are independently H, F, Cl, Br, I, CN, CF3, CHF2, CH2F, OCF3, OCHF2, OCH2F, SCF3, OC 1~4 -Aliphatic residue, C 1~4 -Aliphatic residue, or S(=O) 2- C 1~4- represents an aliphatic residue. In a further embodiment, n represents 1 and A 1 represents N, and A 2 is CR 4 represents A 3 is CR 4 represents A 4 is CR 4 or n represents 1, and A 1 is CR 4 represents A 2 represents N, and A 3 is CR 4 represents A 4 is CR 4 or n represents 1, and A 1 is CR 4 represents A 2 is CR 4 represents A 3 represents N, and A 4 is CR 4 or n represents 1, and A 1 is CR 4 represents A 2 is CR 4 represents A 3 is CR 4 represents A 4 represents N, or n represents 1, and A 1 represents N, and A 2 represents N, and A 3 is CR 4 represents A 4 is CR 4 or n represents 1, and A 1 represents N, and A 2 is CR 4 represents A 3 represents N, and A 4 is CR 4 or n represents 1, and A 1 represents N, and A 2 is CR 4 represents A 3 is CR 4 represents A 4 represents N, or n represents 1, and A 1 is CR 4 represents A2 represents N, and A 3 represents N, and A 4 is CR 4 or n represents 1, and A 1 is CR 4 represents A 2 represents N, and A 3 is CR 4 represents A 4 represents N, or n represents 1, and A 1 is CR 4 represents A 2 is CR 4 represents A 3 represents N, and A 4 represents N or n represents 0, and A 1 is CR 4 represents A 2 is CR 4 represents A 3 represents S or n represents 0, and A 1 represents N, and A 2 is CR 4 represents A 3 represents S or n represents 0, and A 1 represents S, and A 2 is CR 4 represents A 3 is CR 4 or n represents 0, and A 1 represents S, and A 2 is CR 4 represents A 3 represents N.

[0301] In a further embodiment, R 2 is F, Cl, Br, I, CN, CF3, NO2, OCF3, SCF3, C 1~4 -Aliphatic residue, SC 1~4 -aliphatic residue, or OC 1~4 - represents an aliphatic residue, C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, ═O, OH and OC 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues.

[0302] In a further embodiment, R 2 is C 1~4 - represents an aliphatic residue.

[0303] In further embodiments, each R 4 independently represent H, F, Cl, Br, CN, CF3, OCF3, CH3, OCH3, or S(=O)2CH3.

[0304] In a further embodiment, R 1 is a substructure: [ka] wherein m represents 0, 1, or 2; R 1a and R 1b are each independently H, F, Cl, Br, I, OC 1~4 - an aliphatic residue, or C 1~4 - represents an aliphatic residue, and R 1c is unsubstituted or is F, Cl, Br, I, OC 1~4 -aliphatic residues, CF3 and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, CF3 and OC 1~4 -aliphatic residues), C 1~4 - represents an aliphatic residue, or in any case unsubstituted or F, Cl, Br, I, OC 1~4 -aliphatic residues, CF3 and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, CF3 and OC 1~4 -aliphatic residues), C 3~10- represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, or in either case unsubstituted or substituted with F, Cl, Br, I, OH, OC 1~4 -Aliphatic residues, OCF3, CF3, CN, C 1~4 -Aliphatic residues, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, C 3~6 - represents an aryl or heteroaryl mono- or polysubstituted by at least one substituent selected from the group consisting of an alicyclic residue, a 3- to 7-membered heterocyclic aliphatic residue, benzyl, phenyl, thienyl, or pyridyl, wherein benzyl, phenyl, thienyl, and pyridyl are in each case unsubstituted or selected from the group consisting of F, Cl, Br, I, OH, OC 1~4 -Aliphatic residues, OCF3, CF3, CN, C 1~4 an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5; C 3~6 The alicyclic residue and the 3- to 7-membered heterocyclic aliphatic residue are in each case unsubstituted or may be substituted with F, Cl, Br, I, OH, ═O, OC 1~4 -Aliphatic residue, OCF3, CF3, C 1~4 It may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH.

[0305] In a further embodiment, m represents 1 or 2 and R 1a and R 1b represents H, and R 1c is unsubstituted or is F, Cl, Br, I, OC 1~4 -aliphatic residues, CF3 and C 1~4 - mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, C 1~4 - represents an aliphatic residue, or in any case unsubstituted or F, Cl, Br, I, OC 1~4 -aliphatic residues, CF3 and C 1~4 - mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, C3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, or m represents 0, and R 1c is in each case unsubstituted or is substituted with F, Cl, Br, I, OH, OC 1~4 -Aliphatic residues, OCF3, CF3, CN, C 1~4 -Aliphatic residues, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, C 3~6 - represents an aryl or heteroaryl mono- or polysubstituted by at least one substituent selected from the group consisting of an alicyclic residue, a 3- to 7-membered heterocyclic aliphatic residue, benzyl, phenyl, thienyl, or pyridyl, wherein benzyl, phenyl, thienyl, and pyridyl are in each case unsubstituted or substituted with F, Cl, Br, I, OH, OC 1~4 -Aliphatic residues, OCF3, CF3, CN, C 1~4 an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5; C 3~6 - the alicyclic residue and the 3- to 7-membered heterocyclic aliphatic residue are in each case unsubstituted or are substituted with F, Cl, Br, I, OH, ═O, OC 1~4 -Aliphatic residue, OCF3, CF3, C 1~4 - aliphatic residues, and C(=O)OH, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH.

[0306] In a further embodiment, R 3 is unsubstituted or is F, Cl, Br, I, OH, ═O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -aliphatic residues, CF3, CN, and C 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, CF3 and OC 1~4-aliphatic residues), C 2~6 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, Br, I, OH, ═O, OC 1~4 -Aliphatic residue, OCF3, SCF3, (=O)-OC 1~4 -Aliphatic residue, SC 1~4 -aliphatic residues, CF3, CN, and C 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~7 In either case, the alicyclic residue or the 3- to 7-membered heterocyclic aliphatic residue is C 1~4 - optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, CN, and C 1~4 - aliphatic residues, or R 3 is SR 5 OR 6 wherein R 5 and R 6 is in each case unsubstituted or is selected from the group consisting of F, Cl, Br, I, OH, ═O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residue, NH(C 1~4 -aliphatic residue), N(C 1~4 -aliphatic residues)2, CF3, and C 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, CF3 and OC1~4 -aliphatic residues), C 1~8 represents an aliphatic residue, or in each case unsubstituted or F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 -alicyclic residue or 3- to 7-membered heterocyclic aliphatic residue is C 1~4 - can be linked via an aliphatic group, which is then unsubstituted or can be F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, CF3, CN, and C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, with the proviso that R 5 or R 6 represents a 3- to 7-membered heterocyclic aliphatic residue, provided that the 3- to 7-membered heterocyclic aliphatic residue is linked via a carbon atom, or 3 is N(R 7 R 8 ), wherein R 7 is unsubstituted or is F, Cl, Br, I, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, CF3 and OC 1~4-aliphatic residues), C 1~6 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 -alicyclic residue or 3- to 7-membered heterocyclic aliphatic residue is, in either case, C 1~4 - can be linked via an aliphatic group, which is then unsubstituted or can be F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, CN, and C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, with the proviso that R 7 represents a 3- to 7-membered heterocyclic aliphatic residue, provided that the 3- to 7-membered heterocyclic aliphatic residue is linked via a carbon atom, 8 is unsubstituted or is F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, CN, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -C mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues 1~6 - represents an aliphatic residue, or R 7 and R 8along with the nitrogen atoms that connect them, F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, CN, and C 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, CF3 and OC 1~4 -aliphatic residues), and R 7 and R 8 The 3- to 10-membered heterocyclic aliphatic residues formed together with the nitrogen atom connecting them by the formula (I) can be optionally fused with an aryl or heteroaryl, and the aryl or heteroaryl residues thus fused, for their part, are unsubstituted or can be substituted with F, Cl, OH, OC, respectively. 1~4 -Aliphatic residues, OCF3, SCF3, CF3, ON, C 1~4 -Aliphatic residue, C(=O)OH, C 3~6 Alicyclic residues, 3- to 7-membered heterocyclic aliphatic residues, [ka] may be mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, thienyl, and pyridyl; C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl, thienyl and pyridyl being in each case unsubstituted or selected from the group consisting of F, Cl, OH, OC 1~4 -Aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SCF3, CF3, CN, C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH, C 3~6- the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, OH, ═O, OC 1~4 -Aliphatic residues, OCF3, CF3, CN, C 1~4 It may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH.

[0307] In a further embodiment, R 3 is unsubstituted or is F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 - mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, C 2~6 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 the aliphatic residues are in each case unsubstituted or OH or OC 1~4 -substituted or polysubstituted with at least one substituent selected from the group consisting of: 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 In either case, the alicyclic residue or the 3- to 7-membered heterocyclic aliphatic residue is C 1~4 - optionally linked via an aliphatic group, or R 3 is SR 5 OR 6 wherein R 5 and R 6 is in each case unsubstituted or is substituted with F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, CF3 and OC 1~4-aliphatic residues), C 1~6 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 -alicyclic residue or 3- to 7-membered heterocyclic aliphatic residue is in each case unsubstituted C 1~4 - may be linked via an aliphatic group, provided that R 5 or R 6 represents a 3- to 7-membered heterocyclic aliphatic residue, provided that the 3- to 7-membered heterocyclic aliphatic residue is linked via a carbon atom, or 3 is N(R 7 R 8 ), wherein R 7 is unsubstituted or is F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, CF3 and OC 1~4 -aliphatic residues), C 1~6 represents an aliphatic residue, or in any case unsubstituted or F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 -alicyclic residue or 3- to 7-membered heterocyclic aliphatic residue is in each case unsubstituted C 1~4 - may be linked via an aliphatic group, provided that R 7 represents a 3- to 7-membered heterocyclic aliphatic residue, provided that the 3- to 7-membered heterocyclic aliphatic residue is linked via a carbon atom, 8 is the unsubstituted C 1~4 - represents an aliphatic residue, or R 7 and R 8 together with the nitrogen atom connecting them, are unsubstituted or are F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, CN, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, CF3 and OC 1~4 -aliphatic residues), and R 7 and R 8 The 3- to 7-membered heterocyclic aliphatic residues formed by the formula (I) together with the nitrogen atom connecting them may be optionally fused with phenyl or pyridyl, and the phenyl or pyridyl residues thus fused may, for their part, be unsubstituted or may contain F, Cl, OH, OC, respectively. 1~4 -Aliphatic residues, OCF3, SCF3, CF3, CN, C 1~4 - an aliphatic residue, C(=O)OH, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, and pyridyl, C 1~4The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, OH and OC 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl and pyridyl being in each case unsubstituted or selected from the group consisting of F, Cl, OCH3, OCF3, OCH2CH2OH, OCH2CH2OCH3, SCF3, CF3 and C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues.

[0308] In a further embodiment, A 1 , A 2 , and A 3 are independent of each other, CR 4 , N, O, S, or N(CH3), and A 4 is CR 4 or N, n represents 0 or 1, provided that A 1 , A 2 , A 3、 and A 4 At least one of the following is CR 4 If n is 0, then A 1 , A 2 , and A 3 represents O, S, or N(CH3), or n represents 1; then A 1 , A 2 , and A 3 However, independently of each other, CR 4 or N, R 1 is a substructure: [ka] wherein m represents 0, 1, or 2; 1a and R 1b are each independently H, F, Cl, OC 1~4 - an aliphatic residue, or C 1~4 - represents an aliphatic residue, and R 1c is unsubstituted or F, C 1~10- C 1~4 Aliphatic residues, CF3, and C 1~4-Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, CF3 and OC 1~4 -aliphatic residues), C 1~4 - represents an aliphatic residue, or in each case unsubstituted or F, C 1~10- C 1~4 -aliphatic residues, CF3 and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, CF3 and OC 1~4 -aliphatic residues), C 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, or in either case unsubstituted or with F, Cl, OH, OC 1~4 -Aliphatic residues OCF3, CF3, CN, C 1~4 -Aliphatic residues, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, C 3~6 - represents an aryl or heteroaryl group mono- or polysubstituted by at least one substituent selected from the group consisting of an alicyclic residue, a 3- to 7-membered heterocyclic aliphatic residue, benzyl, phenyl, thienyl, or pyridyl, wherein benzyl, phenyl, thienyl, or pyridyl is in each case unsubstituted or is selected from the group consisting of F, Cl, Br, I, OH, OC 1~4 -Aliphatic residues, OCF3, CF3, CN, C 1~4 an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5; C 3~6 -alicyclic residues and 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, OH, ═O, OOC 1~4 -Aliphatic residues, OCF3, CF3, OC1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH, R 2 is F, Cl, Br, I, CN, CF3, NO2, OCF3, SCF3, C 1~4 -Aliphatic residue, SC 1~4 -aliphatic residue, or OC 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are substituted with F, Cl, ═O, OH and OC 1~4 -aliphatic residues), and R 3 is in each case unsubstituted or is substituted with F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 - mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, C 2~6 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 the aliphatic residues are in each case unsubstituted or OH or OC 1~4 -substituted or polysubstituted with at least one substituent selected from the group consisting of: 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, C 3~10 -The alicyclic residue or the 3- to 10-membered heterocyclic aliphatic residue is, in either case, C 1~4 - optionally linked via an aliphatic group, or R 3 is SR 5 OR 6 wherein R 5 and R 6 is in each case unsubstituted or is substituted with F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, OH, CF3 and OC 1~4 -aliphatic residues), C 1~8 - represents an aliphatic residue, or in any case unsubstituted or F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 -alicyclic residue or 3- to 7-membered heterocyclic aliphatic residue is in each case unsubstituted C 1~4 - may be linked via an aliphatic group, provided that R 5 or R 6 represents a 3- to 7-membered heterocyclic aliphatic residue, provided that the 3- to 7-membered heterocyclic aliphatic residue is linked via a carbon atom, or 3 is N(R 7 R 8 ), wherein R 7 is unsubstituted or is F, Cl, OH, ═O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, CF3 and OC 1~4 -aliphatic residues), C 1~8 - represents an aliphatic residue, or in each case unsubstituted or F, Cl, OH, =O, OC1~4 -Aliphatic residue, OCF3, SCF3, C(=O)-OC 1~4 -aliphatic residues, CF3 and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~6 - represents an alicyclic residue or a 3- to 7-membered heterocyclic aliphatic residue, C 3~6 -alicyclic residue or 3- to 7-membered heterocyclic aliphatic residue is in each case unsubstituted C 1~4 - may be linked via an aliphatic group, provided that R 7 represents a 3- to 7-membered heterocyclic aliphatic residue, provided that the 3- to 7-membered heterocyclic aliphatic residue is linked via a carbon atom, 8 is the unsubstituted C 1~4 - represents an aliphatic residue, or R 7 and R 8 together with the nitrogen atom connecting them, are unsubstituted or are F, Cl, OH, =O, OC 1~4 - Aliphatic residues, OCF3, SCF3, CF3, CN, and C 1~4 -Aliphatic residue (C 1~4 The aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, OH, CF3 and OC 1~4 -aliphatic residues), and R 7 and R 8 The 3- to 7-membered heterocyclic aliphatic residues formed by the formula (I) together with the nitrogen atom connecting them may be optionally fused with phenyl or pyridyl, and the phenyl or pyridyl residues thus fused may, for their part, be unsubstituted or may contain F, Cl, OH, OC, respectively. 1~4 -Aliphatic residues, OCF3, SCF3, CF3, CN, C 1~4- an aliphatic residue, C(=O)OH, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, and pyridyl, C 1~4 The aliphatic residues are in each case unsubstituted or are substituted with F, Cl, OH and OC 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl and pyridyl being in each case unsubstituted or selected from the group consisting of F, Cl, OCH3, OCF3, OCH2CH2OH, OCH2CH2OCH3, SH, SCF3, CF3 and C 1~4 - aliphatic residues, each R 4 independently represent H, F, Cl, Br, CN, CF3, OCF3, CH3, OCH3, or S(=O)2CH3.

[0309] In a further embodiment, the Kv7 channel activator is selected from the group consisting of 1 2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,5]naphthyridine-3-carboxylic acid amide, 2 2-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, 4 2-ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,6]naphthyridine-3-carboxylic acid amide, 5 2-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, 7 2-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-[1,8]naphthyridine-3-carboxylic acid amide, 8 2-Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-[1,8]naphthyridine-3-carboxylic acid amide, 9 2-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,8]naphthyridine-3-carboxylic acid amide, 10 2-Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,8]naphthyridine-3-carboxylic acid amide, 11 2-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,6]naphthyridine-3-carboxylic acid amide, 12 2-Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,6]naphthyridine-3-carboxylic acid amide, 13 2-Ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,5]naphthyridine-3-carboxylic acid amide, 14 2-Ethylsulfanyl-N-[(4-fluorophenyl)-methyl]-4-methyl-7-(trifluoromethyl)-[1,5] naphthyridine-3-carboxylic acid amide, 15 5-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-7-methyl-thieno[3,2-b]pyridine-6-carboxylic acid amide, 16 6-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-4-methyl-thieno[2,3-b]pyridine-5-carboxylic acid amide, 17 5-ethoxy-N-[(3-fluorophenyl)-methyl]-7-methyl-2-(trifluoromethyl)-thieno[3,2-b]pyridine-6-carboxylic acid amide, 18 6-ethoxy-N-[(3-fluorophenyl)-methyl]-4-methyl-2-(trifluoromethyl)-thieno[2,3-b]pyridine-5-carboxylic acid amide, in the form of a free compound, a solvate, and / or a physiologically acceptable salt.

[0310] formula 20 In embodiments, the Kv7 channel activator may be selected from one of the following compounds according to Formula 20. Such compounds are described in U.S. Patent No. 9,284,286, published March 15, 2016, corresponding to U.S. Patent Application No. 14 / 091.373, filed November 27, 2013, and International Publication No. WO2014082737A1, published June 5, 2014, corresponding to International Application No. PCT / EP2013 / 003572, filed November 27, 2013, which are incorporated herein by reference in their entireties. In the event of any discrepancy in terminology relating to Formula 20, these references, incorporated herein by reference, shall control.

[0311] In embodiments, the Kv7 channel activator is a compound according to Formula 20: [ka] In the formula, A 1 But, CR 10 R 11 or S, A 2 But, CR 12 R 13 , C(=O), O, S, S(=O), or S(=O)2, and A 3 , A4 , and A 5 However, independently of each other, CR 7 , N, O, S, or NR 8 represents A 6 But, CR 7 or N, where n is 0 or 1, provided that when n is 0, A 3 , A 4 , and A 5 Exactly one of is O, S, or NR 8 or if n is 1, then A 3 , A 4 , and A 5 However, independently of each other, CR 7 or N, where n represents 1, and A 3 , A 4 , and A 5 are respectively, CR 7 If you want to represent 6 does not represent N, and R 1 is unsubstituted or mono- or polysubstituted C 1~10 - an aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~4 - optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, C 3~10 - an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, in each case unsubstituted or mono- or polysubstituted, in each case C 1~4 - represents an aryl or heteroaryl, optionally linked via an aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted, and R 2 , R 3 , R 4 , R 5 , R 10 , R 11 , R 12 , and R 13 are each, independently of one another, H, F, Cl, Br, I, NO2, CF3, CN, OH, OCF3, SH, SCF3, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted, C 1~10 -Alicyclic residue, OC 1~10 -alicyclic residue, or SC1~10 - an alicyclic residue, or a saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted, C 3~10 - represents an alicyclic residue, or R 2 and R 3 , or R 4 and R 5 , or R 10 and R 11 , or R 12 and R 13 , or R 2 and R 11 , or R 2 and R 4 , or R 2 and R 13 , or R 4 and R 13 , or R 4 and R 11 , or R 12 and R 13 are, together with the carbon atom(s) to which they are attached, in each case saturated or unsaturated, unsubstituted or mono- or polysubstituted, C 3~10 - forms an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, and the remaining substituents R 2 , R 3 , R 4 , R 5 , R 10 , R 11 , R 12 , and R 13 in each case has the meaning given above, and R 6 is in each case saturated or unsaturated, unsubstituted or mono- or polysubstituted, C 3~10 - represents an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, or in each case represents an aryl or heteroaryl, which is unsubstituted, monosubstituted or polysubstituted, and each R 7 are, independently of each other, H, F, Cl, CN, CF3, CHF2, CH2F, CF3, OCHF2, OCH2F, SCF3, OC 1~4 -Aliphatic residue, C 1~4 -Aliphatic residue, or S(=O) 2- C 1~4 -Aliphatic residue (C 1~4- aliphatic residues, which in each case may be saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted), and R 8 But H or C 1~4 - represents an aliphatic residue, which may be saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted, "aliphatic group" and "aliphatic residue" in each case may be branched or unbranched, saturated or unsaturated, "alicyclic residue" and "heterocyclic aliphatic residue" in each case may be saturated or unsaturated, and "mono- or poly-substitution" with respect to "aliphatic group", "aliphatic residue", "alicyclic residue" and "heterocyclic aliphatic residue" refers to F, Cl, Br, I, NO, NH, NH(C) with respect to the corresponding residue or group. 1~4 -aliphatic residue), N(C 1~4 -aliphatic residue)2, NH-C(=O)-C 1~4 Aliphatic residue, N(C 1~4 -Aliphatic residue)-C(=O)-C 1~4 -Aliphatic residue, NH-S(=O) 2- C 1~4 -Aliphatic residue, N(C 1~4 -Aliphatic residue)-S(=O) 2- C 1~4 -Aliphatic residues, =O, OH, OCF3, OC 1~4 -Aliphatic residue, OC(=O)-C 1~4 -Aliphatic residues, SH, SCF3, SC 1~4 -Aliphatic residue, S(=O)2OH, S(=O) 2- C 1~4 -Aliphatic residue, S(=O) 2- O.C. 1~4 -Aliphatic residue, S(=O) 2- NH(C 1~4 -aliphatic residue), S(=O) 2- N(C 1~4 -Aliphatic residues)2, CN, CF3, CHO, COOH, C 1~4 -Aliphatic residue, C(=O)-C 1~4 -Aliphatic residue, C(=O)-OC 1~4 -Aliphatic residue, C 3~6 -alicyclic residues, 3-7 membered heterocyclic aliphatic residues, benzyl, aryl, heteroaryl, C(=O)NH2, C(=O)-NH(C 1~4-aliphatic residues), and C(=O)-N(C 1~4 -aliphatic residues)2, and "mono- or polysubstitution" with respect to "aryl" and "heteroaryl" refers to the replacement of one or more hydrogen atoms, each independently of the other, by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, [ka] NH(C 1~4 -aliphatic residue), N(C 1~4 -aliphatic residue)2, NH-C(=O)-C 1~4 -Aliphatic residue, N(C 1~4 aliphatic residue)-C(=O)-C 1~4 -Aliphatic residue, NH-S(=O) 2- C 1~4 Aliphatic residue, N(C 1~4 aliphatic residue)-S(=O) 2- C 1~4 -Aliphatic residues, OH, OCF3, OC 1~4 -Aliphatic residue, OC(=O)-C 1~4 -Aliphatic residues, SH, SCF3, SC 1~4 -Aliphatic residue, S(=O)2OH, S(=O) 2- C 1~4 -Aliphatic residue, S(=O) 2- O.C. 1~4 -Aliphatic residue, S(=O) 2- NH(C 1~4 -aliphatic residue), S(=O) 2- N(C 1~4 -Aliphatic residue)2, CN, CF3, C(=O)H, C(=O)OH, C 1~4 -Aliphatic residue, C(=O)-C 1~4 -Aliphatic residue, C(=O)-OC 1~4 -Aliphatic residue, C 3~6 -alicyclic residues, 3-7 membered heterocyclic aliphatic residues, benzyl, aryl, heteroaryl, C(=O)NH2, C(=O)-NH(C 1~4 -aliphatic residues), and C(=O)-N(C 1~4-aliphatic residues)2, in the form of individual single stereoisomers or mixtures of stereoisomers in any ratio and / or in the form of free compounds, solvates and / or physiologically acceptable salts.

[0312] In a further embodiment, A 1 is CR 10 R 11 or S, A 2 is CR 12 R 13 , C(=O), O, S, S(=O), or S(=O)2, and A 3 , A 4 , and A 5 are independent of each other, CR 7 , N, O, S, or NR 8 represents A 6 is CR 7 or N, where n represents 0 or 1, provided that when n represents 0, A 3 , A 4 , and A 5 Exactly one of is O, S, or NR 8 or if n is 1, then A 3 , A 4 , and A 5 However, independently of each other, CR 7 or N, where n represents 1, and A 3 , A 4 , and A 5 are respectively, CR 7 If you want to represent 6 does not represent N, and R 1 is unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4-C mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH 1~10 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), which may be mono- or polysubstituted with at least one substituent selected from the group consisting of: F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residue, C(=O)-OH, C 3~6 -alicyclic residues and 3- to 7-membered heterocyclic aliphatic residues (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - aliphatic residues, C 3~6 - the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH (which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH), 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue (C 3~10 -The alicyclic residue or the 3- to 10-membered heterocyclic aliphatic residue is, in either case, C 1~4- optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH), or in each case unsubstituted or with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residues)2, OH, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residues, C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, C 3~6 Alicyclic residues, 3- to 6-membered heterocyclic aliphatic residues, [ka] represents an aryl or heteroaryl mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl, and oxazolyl; C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, which in each case may be unsubstituted or may be selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residues)2, OH, OC 1~4 -Aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, SC 1~4-Aliphatic residues, CF3, CN, C 1~4 aliphatic residues, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, C 3~6 - the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues and C(=O)OH, and the aryl or heteroaryl residue may in each case be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH. 1~4 - optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 - aliphatic residues, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of CF3, CN, and C(=O)OH, R 2 , R 3 , R 5 , R 10 , R 11 , R 12 , and R 13 are each independently H, F, Cl, Br, I, NO2, CF3, CN, OH, OCF3, SH, SCF3, in each case saturated or unsaturated, branched or unbranched, C 1~4 -Aliphatic residue, OC 1~4 -aliphatic residue, or SC 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4-aliphatic residues), or saturated or unsaturated, branched or unbranched, in each case unsubstituted or substituted with F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -aliphatic residues, and C(=O)OH(C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), C 3~10 - represents an alicyclic residue, C 3~10 -alicyclic residues are in each case C 1~4 - optionally substituted via an aliphatic group, which in turn is unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -C, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH; 1~4 - optionally substituted via an aliphatic group, or R 2 and R 3 , or R 4 and R 5 , or R 10 and R 11 , or R 12 and R 13 , or R 2 and R 11 , or R 2 and R 4 , or R 2 and R13 , or R 4 and R 13 , or R 4 and R 11 , or R 12 and R 13 together with the carbon atom(s) connecting them, may in each case be saturated or unsaturated, and in each case unsubstituted or substituted with F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic group, CF3, CN, C 1~4 -C mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH; 3~10 - forms an alicyclic residue or a 3- to 10-membered heterocyclic aliphatic residue, C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - aliphatic residues, C 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue is C 1~4 - optionally linked via an aliphatic group, which is then in each case unsubstituted or substituted with F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues and C(=O)OH, and the remaining substituents R 2 , R 3 , R 4 , R 5 , R 10 , R 11 , R 12 , and R 13has in each case the meaning given above, and R 6 is in each case saturated or unsaturated, in each case unsubstituted or substituted with F, Cl, Br, I, NO, NH, NH(C 1~4 -Aliphatic residue, N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residue, C(=O)OH, C 3~6 -alicyclic residues and 3- to 7-membered heterocyclic aliphatic residues (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - aliphatic residues, C 3~6 - the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues, and C(=O)OH (which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH), 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue (C 3~10 -alicyclic residue or 3- to 10-membered heterocyclic aliphatic residue is C 1~4 - optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4- aliphatic residues, and C(=O)OH), or in each case unsubstituted or with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 -Aliphatic residues, C(=O)OH, C(=O)CH3, C(=O)C2H5, C(=O)OCH3, C(=O)OC2H5, C 3~6 -alicyclic residue, 3- to 7-membered heterocyclic aliphatic residue, [ka] represents an aryl or heteroaryl mono- or polysubstituted with at least one substituent selected from the group consisting of benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl, and oxazolyl; C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues, benzyl, phenyl, thienyl, pyridyl, furyl, thiazolyl and oxazolyl, which in each case may be unsubstituted or may be selected from the group consisting of F, Cl, Br, I, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, OC 1~4 -Aliphatic residues, OCF3, OCH2CH2OH, OCH2OCH3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 an aliphatic residue, which may be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH, (=O)CH3, C(=O)C2H5, C(=O)OCH3, and C(=O)OC2H5; 3~6- the alicyclic residues and the 3- to 7-membered heterocyclic aliphatic residues are in each case unsubstituted or are substituted with F, Cl, Br, I, NO2, NH2, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 -Aliphatic residues, CF3, CN, C 1~4 - aliphatic residues and C(=O)OH, and the aryl or heteroaryl residue may in each case be mono- or polysubstituted with at least one substituent selected from the group consisting of C(=O)OH. 1~4 - optionally linked via an aliphatic group, which is then unsubstituted or is selected from the group consisting of F, Cl, Br, NO, NH, NH(C 1~4 -aliphatic residue), N(C 1~4 -Aliphatic residue)2, OH, =O, OC 1~4 -Aliphatic residues, OCF3, SH, SCF3, SC 1~4 - aliphatic residues, may be mono- or polysubstituted with at least one substituent selected from the group consisting of CF3, CN, and C(=O)OH, and each R 7 are, independently of each other, H, F, Cl, CN, CF3, CHF2, CH2F, OCF3, OCHF2, OCH2F, SCF3, OC 1~4 -Aliphatic residue, C 1~4 -Aliphatic residue, or S(=O) 2- C 1~4 -Aliphatic residue (C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 -aliphatic residues), and R 8 is H or C 1~4 - represents an aliphatic residue, C 1~4 aliphatic residues are in each case unsubstituted or are selected from the group consisting of F, Cl, Br, I, OH, OCF3, CF3 and OC 1~4 - may be mono- or polysubstituted with at least one substituent selected from the group consisting of aliphatic residues.

[0313] In a further embodiment, A 1 represents S, and A 2 is S, S(=O)2, or CR 12 R 13 wherein R 12 and R 13 both represent H or both represent F.

[0314] In a further embodiment, n represents 1 and A 3 is CR 7 represents A 4 is CR 7 represents A 5 is CR 7 represents A 6 is CR 7 or n represents 1, and A 3 represents N, and A 4 is CR 7 represents A 5 is CR 7 represents A 6 is CR 7 or n represents 1, and A 3 is CR 7 represents A 4 represents N, and A 5 is CR 7 represents A 6 is CR 7 or n represents 1, and A 3 is CR 7 represents A 4 is CR 7 represents A 5 represents N, and A 6 is CR 7 or n represents 1, and A 3 represents N, and A 4 represents N, and A 5 is CR 7 represents A 6 is CR 7 or n represents 1, and A 3 represents N, and A 4 is CR 7 represents A 5 represents N, and A 6 is CR7 or n represents 1, and A 3 represents N, and A 4 is CR 7 represents A 5 is CR 7 represents A 6 represents N, or n represents 1, and A 3 is CR 7 represents A 4 represents N, and A 5 is CR 7 represents A 6 represents N, or n represents 1, and A 3 is CR 7 represents A 4 represents N, and A 5 represents N, and A 6 is CR 7 or n represents 1, and A 3 is CR 7 represents A 4 is CR 7 represents A 5 represents N, and A 6 represents N or n represents 0, and A 3 represents S, and A 4 is CR 7 represents A 5 is CR 7 or n represents 0, and A 3 represents S, and A 4 is CR 7 represents A 5 represents N or n represents 0, and A 3 represents O, and A 4 is CR 7 represents A 5 is CR 7 or n represents 0, and A 3 is CR 7 represents A 4 is CR 7 represents A 5 represents N or n represents 0, and A 3 is CR 7 represents A 4 is CR 7 represents A 5represents S or n represents 0, and A 3 represents N, and A 4 is CR 7 represent...

Claims

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

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

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

6. 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. 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 200-260.

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

9. the metal channel activator is 【Chemical 1】 The pharmaceutical composition according to any one of claims 1 to 8, wherein

10. the metal channel activator 【Chemistry 2】 The pharmaceutical composition according to any one of claims 1 to 8, wherein

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

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

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

15. The prodrug of lanicemine has the following structure: 【Chemistry 3】 (Wherein R1 is C １～６ Alkyl C(O)O(C １～６ alkoxy), or 【Chemistry 4】 15. The pharmaceutical composition of claim 14, comprising: (AA) or a pharmaceutically acceptable salt thereof, wherein AA is a natural amino acid linked by a peptide bond.

16. The prodrug of lanicemine has the following structure: 【Chemistry 5】 or a pharmaceutically acceptable salt thereof.

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

18. 18. The method of claim 17, wherein the depressive disorder is major depressive disorder (MDD), severe 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 response, or a combination thereof.

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

20. The neurological or neurodegenerative disorder is amyotrophic lateral sclerosis, bipolar disorder, treatment-resistant depression and major depression, generalized anxiety disorder, panic disorder, social anxiety, mood disorder, cognitive impairment, dementia, agitation, apathy, psychosis, post-traumatic stress disorder, irritability, disinhibition, learning disability, memory loss, personality disorder, bipolar disorder, Rett syndrome, eating disorder, conduct disorder, neurodegenerative disorder, pain disorder, supranuclear palsy, frontotemporal dementia, frontotemporal lobar degeneration, delirium, Alzheimer's disease, 20. The method of claim 19, wherein the condition is caused by 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's syndrome, autism spectrum disorder, schizophrenia, fragile X syndrome, Parkinson's disease, Huntington's disease, or any combination thereof.

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

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

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

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

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

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