title: X-ray crystal structure and conformational analysis of N-(3-dimethylaminopropyl)-N-(ethylaminocarbonyl)-6-(2-propenyl)er goline -8 beta-carboxamide (Cabergoline): comparison with bromocriptine and lisuride and a hypothesis for its high dopaminergic activity.
abstract: The crystal structure of Cabergoline, a potent and long lasting prolactin lowering agent interacting with the D2 dopamine receptors, has been determined by X-ray diffraction data. The structural data represent the starting point for a computational study, where the molecular mechanisms approach was used to explore the motion of all unconstrained torsion angles. Two different conformations related to energetic minima have been found, one of them in agreement with the experimental crystal structure. Both conformations are shape compared with Bromocriptine and Lisuride, two dopaminergic ergoline derivatives with C-8 beta and C-8 alpha substituents of the ergoline ring, respectively. We observe that the C-8 beta Cabergoline assumes the overall three-dimensional features of C-8-alpha-ergolines in one of its low-energy conformations.
authors.affiliation: Dipartimento di Chimica G. Ciamician, Università di Bologna, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Sabatino
authors.forename: L
authors.initials: L
authors.lastname: Riva di Sanseverino
authors.forename: R
authors.initials: R
authors.lastname: Tonani
mesh_terms: D001971:Bromocriptine / Q000737:chemistry* / Q000494:pharmacology; D000077465:Cabergoline; D018360:Crystallography, X-Ray; D018491:Dopamine Agonists / Q000737:chemistry* / Q000494:pharmacology; D004873:Ergolines / Q000737:chemistry* / Q000494:pharmacology; D008090:Lisuride / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D001971:Bromocriptine; D008090:Lisuride; D000077465:Cabergoline