title: Semi-rigid analogues of the calcium antagonist verapamil: a molecular modelling study.
abstract: In this work the rigid-analogue approach has been used to obtain information on the active conformation(s) of the calcium antagonist verapamil. A series of semi-rigid analogues of verapamil were synthesized and their biological activities evaluated on guinea-pig heart and aorta. These molecules were analysed by means of molecular modelling techniques. On the basis of the pharmacological profile and conformational analysis of these compounds, two different models for negative inotropic and negative chronotropic activity are proposed. The two actions seem to be due to conformations of the molecules which differ in the orientation of their phenylethylamino groups.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
authors.forename: M N
authors.initials: MN
authors.lastname: Romanelli
authors.forename: S
authors.initials: S
authors.lastname: Dei
authors.forename: S
authors.initials: S
authors.lastname: Scapecchi
authors.forename: E
authors.initials: E
authors.lastname: Teodori
authors.forename: F
authors.initials: F
authors.lastname: Gualtieri
authors.forename: R
authors.initials: R
authors.lastname: Budriesi
authors.forename: R
authors.initials: R
authors.lastname: Mannhold
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D003196:Computer Graphics; D015195:Drug Design; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D014700:Verapamil