title: Synthesis and antihistaminic activity of 2-guanadino-3-cyanopyridines and pyrido[2,3-d]-pyrimidines.
abstract: 2-Guanadino-3-cyanopyridines 8-33 and pyrido[2,3-d]-pyrimidines 35-52 were synthesized by nucleophilic displacement and cyclization of the chloroamidines 6a-d easily obtained by reaction of 2-aminocyanopyridines 5a-d with phosgene iminium chloride and their action on the release of histamine by mast cells examined under immunological and chemical stimulus, with and without pre-incubation. Several 2-guanadino-3-cyanopyridines and pyrido[2,3-d]-pyrimidines are shown to be inhibitors of the release of histamine when stimulated with ovoalbumin as antigen or with polymer 48/80 as chemical stimulus. Guanadino-3-cyanopyridine 30 and pyrido[2,3-d]-pyrimidine 49 are the more active of all, inhibiting the release of histamine in all the conditions tested (30-60% inhibition). Guanadinocyanopyridines 15, 17, and 19 are very potent stimulators of the release of histamine (150-300%) while pyrido[2,3-d]-pyrimidines are mostly inactive. Compounds 28 and 14 present moderate in vitro cytotoxic activity against P-388, A-549, HT-29, and MEL-28 cell lines.
authors.affiliation: Departamento de Química Fundamental e Industrial, Facultad de Ciencias, Universidad de La Coruña, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Quintela
authors.forename: C
authors.initials: C
authors.lastname: Peinador
authors.forename: L
authors.initials: L
authors.lastname: Botana
authors.forename: M
authors.initials: M
authors.lastname: Estévez
authors.forename: R
authors.initials: R
authors.lastname: Riguera
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D008956:Models, Chemical; D011725:Pyridines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D006634:Histamine H1 Antagonists; D011725:Pyridines; D011743:Pyrimidines; C020729:3-cyanopyridine