The crystal and molecular structures of the dopaminergic ergoline derivative pergolide have been determined both as the free base and as the mesylate salt. Despite differences in protonation at the nitrogen atom, the two structures are extremely similar in all aspects. Stereochemical comparisons are made with bromocriptine, and possible dopaminergic pharmacophores in ergolines are discussed.
In the crystal structure of the title dopaminergic compound, C16H24NO2+.Br-.H2O, protonation occurs at the piperidine N atom. The piperidine ring adopts a chair conformation and the cyclohexene ring adopts a half-chair conformation; together with the planar benzene ring, this results in a relatively planar shape for the whole molecule. Classical hydrogen bonds (N-H...Br, O-H...Br and O-H...O) produce an infinite three-dimensional network. Hydrogen bonds between water molecules and Br- anions create centrosymmetric rings throughout the crystal structure. Structural comparison of the molecule with the ergoline dopamine agonist pergolide shows that it is the hydrogen-bond-forming hydroxy or imino group that is necessary for dopaminergic activity, rather than the presence of a phenyl or a pyrrole ring per se.
In the title compound, C15H14N4S, the outer phenyl ring makes an angle of 101.4 (2)° with the plane through the inner benzene ring, and the planes of the thiadiazole ring and the attached benzene ring intersect at an angle of 146.7 (2)°. In addition to weak N—H⋯N hydrogen bonds, creating a two‐dimensional network parallel to the bc plane of the crystal structure, there is also one non‐standard hydrogen‐bond interaction of the type C—H⋯N. Stereochemical comparison with the closely related compound 1‐[5‐(biphenyl‐2‐yl)‐1,3,4‐thiadiazol‐2‐yl]methanaminium chloride shows that the two compounds utilize the same mechanism for anticonvulsant activity.
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