title: Structural features of some diphenhydramine analogues that determine the interaction with rat liver cytochrome P-450.
abstract: The aim of this study was to define the structural characteristics in a series of 21 analogues of the anti-histaminergic drug diphenhydramine which are important for the interaction with cytochrome P-450. The compounds gave substrate (type I) binding spectra with rat hepatic microsomal cytochrome P-450. The main findings were: (1) two phenyl rings are needed for strong binding: saturation or elimination of one ring, or restriction of two phenyls with a two-carbon bridge results in a decrease of binding, (2) substitution on one or both aromatic rings has only a small influence on binding, (3) an amine nitrogen contributes to better binding; decrease or absence of basicity weakens binding, and (4) a chain of 4 to 7 atoms connecting the basic centre with the aromatic part is needed; reduction of the chain length, or restriction of it to a cyclic structure causes decrease or loss of binding ability.
authors.affiliation: Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Rekka
authors.forename: H
authors.initials: H
authors.lastname: Timmermann
authors.forename: A
authors.initials: A
authors.lastname: Bast
mesh_terms: D000818:Animals; D001665:Binding Sites; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004155:Diphenhydramine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D004155:Diphenhydramine; D003577:Cytochrome P-450 Enzyme System