title: Synthesis and antiallergic activity of pyridothienopyrimidines.
abstract: The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor 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: C
authors.initials: C
authors.lastname: Veiga
authors.forename: L
authors.initials: L
authors.lastname: González
authors.forename: L M
authors.initials: LM
authors.lastname: Botana
authors.forename: A
authors.initials: A
authors.lastname: Alfonso
authors.forename: R
authors.initials: R
authors.lastname: Riguera
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: C116528:4-(4-acetylphenyl)piperazino-7,9-diphenylpyrido(3',2'-4,5)thieno(3,2-d)pyrimidine; D018926:Anti-Allergic Agents; D000970:Antineoplastic Agents; D011743:Pyrimidines; D013876:Thiophenes; D006632:Histamine; D010047:Ovalbumin; D004205:Cromolyn Sodium