title: Synthesis and preliminary biological evaluation of novel N-substituted 1-amino-3-[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols interesting as potential antiarrhythmic, local anaesthetic and analgesic agents.
abstract: A series of indazoloxypropanolamines 7 and 8, pindolol isosteres, were synthesized to extend the structure activity relationship (SAR) which was observed in an earlier series of related derivatives. Compounds 7, characterized by methyl substitution on the N-1 indazole nucleus, generally exhibited significant antiarrhythmic, local anaesthetic and analgesic activities. The preliminary radioligand binding assay highlighted, in compounds 7, an interesting beta 1-affinity which can be well correlated to their antiarrhyhtmic activity. Analogues 8 characterized by a phenyl group on the N-1 indazole nucleus, were generally less active as antiarrhyhtmic agents but generally interesting as local anaesthetics. Due to the importance of the indazole moiety as a carrier of antiphlogistic activity, the two classes of derivatives 7 and 8 were evaluated for their NSAID behaviour. Once again, compounds 7 resulted having more interesting analgesic and antipyretic effects than analogues 8.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mosti
authors.forename: G
authors.initials: G
authors.lastname: Menozzi
authors.forename: P
authors.initials: P
authors.lastname: Fossa
authors.forename: W
authors.initials: W
authors.lastname: Filippelli
authors.forename: S
authors.initials: S
authors.lastname: Gessi
authors.forename: B
authors.initials: B
authors.lastname: Rinaldi
authors.forename: G
authors.initials: G
authors.lastname: Falcone
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology; D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D010975:Platelet Aggregation Inhibitors; D018340:Receptors, Adrenergic, alpha-1; D001569:Benzodiazepines