Substituted 2-[2-(phenyl) ethylamino] alkaneamide derivatives and their use as sodium and/or calcium channel modulators
Inventors
Melloni, Piero • Restivo, Alessandra • Izzo, Emanuela • Francisconi, Simona • Colombo, Elena • Sabido-David, Cibele
Assignees
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Publication Number
US-9051240-B2
Publication Date
2015-06-09
Expiration Date
Abstract
Substituted 2-[2-(phenyl)ethylamino]alkaneamide derivatives, pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing them are useful as sodium and/or calcium channel modulators for preventing, alleviating and curing pathologies wherein the above mechanisms play a pathological role. The compounds may be particularly useful for the prevention, alleviation, and curing of, for example, neurological, cognitive, psychiatric, inflammatory, urogenital and gastrointestinal diseases.
Core Innovation
Substituted 2-[2-(phenyl)ethylamino]alkaneamide derivatives are described as voltage-dependent sodium and/or calcium channel blockers/modulators. A general chemical formula (I) is provided with detailed substituent definitions, including stereoisomers and pharmaceutically acceptable salts.
The disclosure addresses compounds that modulate voltage-gated sodium and/or voltage-gated calcium channels while minimizing MAO-related dietary and pharmacological side effects. The compounds are stated to be substantially free of MAO inhibitory activity or to have reduced MAO inhibition, and MAO-B is measured in vitro as part of the evaluation.
Pharmacological characterization is described using sodium influx, patch clamp, and calcium influx assays, together with in vitro MAO-B measurement and in vivo testing. The document also includes extensive lists of formula (I) compounds, including a representative highly active compound (NW-3509), and experimental model descriptions spanning cognitive, psychiatric, pain, anticonvulsant, migraine-related, and urological disorder tests.
Claims Coverage
One inventive feature is identified across the input items.
Administering formula I for cognitive or psychiatric disorders
A method for treating a cognitive or psychiatric disorder by administering to a patient in need thereof an effective amount of a compound of formula (I), including pharmaceutically acceptable salts and isolated optical isomers or mixtures of optical isomers.
The claim coverage centers on administering compounds of formula (I) for cognitive or psychiatric disorders, with the compounds defined to include pharmaceutically acceptable salts and optical isomers.
Stated Advantages
Compounds are substantially free of MAO inhibitory activity, or have reduced MAO inhibition, to avoid MAO-related dietary and pharmacological side effects.
Compounds are described as voltage-dependent sodium and/or calcium channel blockers/modulators.
Documented Applications
Preventing, alleviating, and treating cognitive or psychiatric disorders selected from Mild Cognitive Impairment (MCI) and cognitive disorders associated with autism, dyslexia, attention deficit hyperactivity disorder, schizophrenia, obsessive compulsive disorder, psychosis, bipolar disorder, depression, Tourette's syndrome, learning disorders, Age Associated Memory Impairment, Age Associated Cognitive Decline, Alzheimer's Disease, Parkinson's Disease, Down's Syndrome, traumatic brain injury, Huntington's Disease, Progressive Supranuclear Palsy (PSP), HIV, stroke, vascular diseases, Pick's or Creutzfeldt-Jacob disease, multiple sclerosis (MS), and drug-induced cognitive worsening.
Preventing, alleviating, and treating psychiatric disorders selected from major depression, apathy, dysthymia, mania, bipolar disorder, cyclothymic disorder, rapid cycling, ultradian cycling, hypomania, schizophrenia, schizophreniform disorder, schizoaffective disorder, personality disorder, attention disorders with or without hyperactive behavior, delusional disorder, brief psychotic disorder, shared psychotic disorder, substance-induced psychotic disorder, anxiety disorders, panic disorder, post-traumatic stress disorder, impulse control disorder, phobic disorder, smoke and drug addiction and alcoholism.
Compounds are described for neurological, inflammatory, urogenital, and gastrointestinal pathologies.
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