title: Conformational analyses on histamine H2-receptor antagonists.
abstract: In a series of compounds with H2-antihistaminic activity, a conformational analysis was performed based on force field calculations. The drugs studied were cimetidine, ranitidine, famotidine, roxatidine and the conformationally more restricted ICI127032. For the compounds containing a flexible chain, the local minima conformations and the global minimum conformation were calculated. These conformations were used for a systematic structural comparison with all energetically allowed conformations of the ICI derivative, with regard to the best fit of the common structural features. In this way a pharmacophore could be developed consisting of four parts: (1) a polar planar group, uncharged at physiological pH; (2) a hydrophobic part formed by aromatic systems or flexible chains; (3) an--under physiological conditions--protonated nitrogen atom; and (4) a substructure, which contains a hydrogen bond donor site and a hydrogen bond acceptor site in a specific spatial arrangement.
authors.affiliation: Institute of Pharmacy, Free University of Berlin, Germany.
authors.forename: H D
authors.initials: HD
authors.lastname: Höltje
authors.forename: A
authors.initials: A
authors.lastname: Batzenschlager
mesh_terms: D001665:Binding Sites; D006635:Histamine H2 Antagonists / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011970:Receptors, Histamine H2 / Q000737:chemistry; D012984:Software
chemical_list: D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2