title: [(3-carboxamidino-2-oxo-2H-chromen-7-yl)-4-guanidinobenzoates are novel blockers of pH-sensitive ion channels].
abstract: Ischemic stroke is one of the most severe brain pathologies that is extremely difficult to treat. Recently it has been found that acidosis accompanying cerebral ischemia induces activation of acid-sensing ion channel ASIC1a which results in its turn in the neuronal death. Here we present novel derivatives of 3-carboxamidinocoumarines that effectively inhibit ASIC1a and ASIC3 channels in concentration-dependent manner. The most active compound inhibits ASIC1a and ASIC3 channels with corresponding IC50 of 7.3 and 13.2 microM. Our data suggest that 3-carboxamidinocoumarines can be used as a scaffold for novel type of highly efficient anti-ischemic drugs.
authors.forename: V A
authors.initials: VA
authors.lastname: Sukach
authors.forename: A Z
authors.initials: AZ
authors.lastname: Buta
authors.forename: O P
authors.initials: OP
authors.lastname: Maksymiuk
authors.forename: D B
authors.initials: DB
authors.lastname: Koval's'kyĭ
authors.forename: M V
authors.initials: MV
authors.lastname: Vovk
authors.forename: O O
authors.initials: OO
authors.lastname: Kryshtal'
mesh_terms: D062565:Acid Sensing Ion Channels; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005727:Ganglia, Spinal / Q000166:cytology; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels
chemical_list: C568266:ASIC1 protein, human; C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D001565:Benzoates; D001578:Benzopyrans; D006146:Guanidines; D009419:Nerve Tissue Proteins; D015222:Sodium Channels