Novel bronchodilatory quinazolines and quinoxalines: synthesis and biological evaluation.
A series of heterocyclic derivatives analogous to (-)vasicinone, in which the vasicinone C-ring was replaced with alkyl chain terminated by tertiary amine was prepared. N3, C4-O, C4-S or C4-N were used as the sites of attachment. The 4-[3-(1-piperidyl)propylsulfanyl]derivatives displayed bronchodilatory effect at low micromolar concentrations on isolated rat trachea, and low toxicity both on Balb/c 3T3 mouse fibroblast cells and in mice.
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic.
Marcel
M
Špulák
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic. Electronic address: pourova@faf.cuni.cz.
Jana
J
Pourová
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic.
Marie
M
Vopršálová
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic.
Jiří
J
Mikušek
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic.
Jiří
J
Kuneš
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc 77515, Czech Republic.
Jan
J
Vacek
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic.
Mukund
M
Ghavre
School of Chemical Sciences and National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.
Nicholas
N
Gathergood
Department of Inorganic and Organic Chemistry, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, CZ-500 03 Hradec Králové, Czech Republic. Electronic address: pour@faf.cuni.cz.
Milan
M
Pour
D016475:3T3 Cells; D000818:Animals; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
D001993:Bronchodilator Agents; D011799:Quinazolines; D011810:Quinoxalines
Bronchodilator; Quinazoline; Synthesis; Toxicity; Vasicinone