title: Synthesis and biological activity of novel substituted benzanilides as potassium channel activators. V.
abstract: As part of our program toward designing potassium channel openers, the synthesis of a novel series of substituted benzanilides and their vasodilating activity are presented. The facile synthetic pathway generally involves coupling between the appropriate benzoyl chloride and commercial available anilines, followed by the selective or non-selective cleavage of methyl ether substituent(s), affording the corresponding phenol or bisphenol derivatives. The pharmacological evaluation of these structurally novel potential BK-openers on vascular contractile activity was studied in vitro, using isolated rat aortic rings pre-contracted with KCl 20 mM. Some derivatives were found to be potent smooth muscle relaxants and the vasodilation effects of these compounds were inhibited by tetraethylammonium (TEA) and iberiotoxin (IbTX), suggesting that the opening of BK channels is prevalent in the mechanism of action of these compounds. The best compound of the series was N-(2-hydroxy-5-phenyl)-(2-methoxy-5-chloro)-benzamide (16b) showing a full vasorelaxant efficacy and almost nanomolar potency index.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Biagi
authors.forename: Irene
authors.initials: I
authors.lastname: Giorgi
authors.forename: Oreste
authors.initials: O
authors.lastname: Livi
authors.forename: Antonio
authors.initials: A
authors.lastname: Nardi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinotti
authors.forename: Oreste
authors.initials: O
authors.lastname: LeRoy Salerni
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology; D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D001565:Benzoates / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008297:Male; D015394:Molecular Structure; D009126:Muscle Relaxation / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry; D015221:Potassium Channels / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000813:Anilides; D000814:Aniline Compounds; D001565:Benzoates; D010455:Peptides; D010636:Phenols; D015221:Potassium Channels; D014665:Vasodilator Agents; D019789:Tetraethylammonium; C064719:iberiotoxin; C034595:benzanilide; C023650:aniline; C013409:benzoyl chloride