title: Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents.
abstract: A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]-5-vinylpyridazin-3(2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with α2-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds.
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Vergelli
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ciciani
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cilibrizzi
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Crocetti
authors.affiliation: NEUROFARBA, Sezione di Farmacologia e Tossicologia, Università degli Studi di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: NEUROFARBA, Sezione di Farmacologia e Tossicologia, Università degli Studi di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guerrini
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Iacovone
authors.affiliation: NEUROFARBA, Sezione di Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Firenze, Italy. Electronic address: mariapaola.giovannoni@unifi.it.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Giovannoni
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000284:Administration, Oral; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D011724:Pyridazines / Q000737:chemistry; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D006571:Heterocyclic Compounds; D011724:Pyridazines; D015016:Yohimbine; D019342:Acetic Acid
keywords: Adrenergic system; Antinociception; Synthesis