Kurzmitteilungen: Synthesis and Biological Evaluation of 3‐(2‐Aminoethyl)pyrrole Derivatives Synthese und biologische Bewertung von 3‐(2‐Aminoethyl)pyrrol‐Derivaten

Abstract

The ergolines are an important class of dopamine receptor agonists'), and the identification of their dopaminergic phannacophore has been sought as a means of developing "purer" agonists r e l M to these structures*).Ergolines combine a phenethylamine and a pyrroleethylamine moiety, both of which have been proposed as the dopaminergic pharmacophores of the molecule^^'^'. Support for these postulates is the fact that certain simplified partial ergoline st~uctures~'~) show potent dopamine agonist activities.The simple 3-(2-amincethyl)pyrrole was also synthesized6) but it was found inen as a dopamine receptor agonist. This inactivity was rationalized on the basis that this primary amino compound is rapidly destroyed in vivo by monoamine oxidases".In this study, compounds la-c were examined for dopamine receptor agonist activities. These compounds are tertiary amines, which would be refractory to monoamine oxidases. Other features which could further maximize the dopamine agonist effects are: a) the n-propyl groups as substituents on the basic nitrogen7), and b) the increased acidity" of the pyrrole NH hydrogens as well as the increased bulkiness of the aromatic area9) in compounds lb-c. ChemistryCompound la was synthesized as described'). The Vilsmeier-Haack acylations") of l a were employed as a method of synthesizing l b c . These reactions gave mixtures of 2-and 5-acyl isomers in approximate ratios of 25/75 (acetylation) and 15/85 (benzoylation) based on 'H-NMR data.