title: 1,8-Naphthyridines IX. Potent anti-inflammatory and/or analgesic activity of a new group of substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides, of some their Mannich base derivatives and of one novel substituted 5-amino-10-oxo-10H-pyrimido[1,2-a][1,8]naphthyridine-6-carboxamide derivative.
abstract: A new group of 5-(alkylamino)-9-isopropyl[1,2,4]triazolo[4,3-a][1,8]naphthyridine derivatives bearing a CONHR group at the 6-position (1c-g), designed to obtain new effective analgesic and/or anti-inflammatory agents, were synthesized and tested along with three new 9-alkyl-5-(4-alkyl-1-piperazinyl)-N,N-diethyl [1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides (2b-d). Besides, a new class of analogues of compounds 1 and 2, bearing a Mannich base moiety at the 9-position (12a-d), as well as the novel N,N-diethyl-5-(isobutylamino)-8-methyl-10-oxo-10H-pyrimido[1,2-a][1,8]naphthyridine-6-carboxamide (15) were prepared and tested. Compounds 1c-g exhibited very interesting anti-inflammatory properties in rats, whereas compounds 2b-d and 15 proved to be endowed with prevalent analgesic activity frequently associated with sedative effects in mice. On the contrary, the Mannich bases 12a-d resulted inactive. The most effective (80% inhibition of oedema) and potent (threshold dose 1.6 mg kg(-1) with 31% inhibition of oedema) anti-inflammatory compound 1d did not show gastrolesive effects following 100 mg kg(-1) oral administration in rats.
authors.affiliation: Dipartimento di Farmacia, Sezione di Chimica del Farmaco e del Prodotto Cosmetico, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova, Genova, Italy. Electronic address: dbraccio@unige.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Di Braccio
authors.affiliation: Dipartimento di Farmacia, Sezione di Chimica del Farmaco e del Prodotto Cosmetico, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova, Genova, Italy. Electronic address: grossig@unige.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Grossi
authors.affiliation: Dipartimento di Farmacia, Sezione di Chimica e Tecnologie Farmaceutiche e Alimentari, Università di Genova, Via Brigata Salerno, 13, I-16147 Genova, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Alfei
authors.affiliation: Dipartimento di Farmacia, Università di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy.
authors.forename: Vigilio
authors.initials: V
authors.lastname: Ballabeni
authors.affiliation: Dipartimento di Farmacia, Università di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Tognolini
authors.affiliation: Dipartimento di Farmacia, Università di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Flammini
authors.affiliation: Dipartimento di Farmacia, Università di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Giorgio
authors.affiliation: Dipartimento di Farmacia, Università di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bertoni
authors.affiliation: Dipartimento di Farmacia, Università di Parma, Parco Area delle Scienze 27/A, I-43124 Parma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Barocelli
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006168:Guinea Pigs; D008124:Locomotion / Q000187:drug effects*; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009287:Naphthyridines; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; D002351:Carrageenan
keywords: 10H-pyrimido[1,2-a][1,8]naphthyridines; Analgesic; Anti-inflammatory; Gastrolesivity; [1,2,4]Triazolo[4,3-a][1,8]naphthyridines