title: Structure-activity relationships and effects of platelet-activating factor antagonists in the hetrazepine series.
abstract: Thieno-triazolo-1,4-diazepines (hetrazepines) antagonize platelet-activating factor (PAF) induced platelet aggregation and inhibit the binding of [3H]-PAF. Introduction of a carboxamide alkyl side chain into the thiophene ring leads to compounds with less affinity to the benzodiazepine receptor and without sedative effects on the central nervous system (e.g., WEB 2086). By ring closure of the side chain, new tetracyclic compounds have been obtained. A parabolic relationship between either [3H]-PAF binding or PAF activity and the bulkiness of the alkyl substituents to the triazolo ring of the hetrazepines or of the bulkiness the 2-acyl moiety of the PAF analogues was found in quantitative structure-activity relationships. This suggests that perhaps the alkyl substituent of the hetrazepines fits the same receptor pocket as the 2-acyl moiety of the PAF agonists.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim KG, Ingelheim, FRG.
authors.forename: K H
authors.initials: KH
authors.lastname: Weber
authors.forename: H
authors.initials: H
authors.lastname: Heuer
mesh_terms: D001381:Azepines / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles
chemical_list: D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014227:Triazines; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086