Profil psychopharmacologique d'un nouvel agoniste Dopaminergique, le RU 24213

Boissier, Jacques R.; Dumont, C; Laurent, J.; Oberlander, Claude

doi:10.1007/bf00426644

Cited by 10 publications

References 16 publications

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

Demopoulos

Tani

Long

1989

Archiv der Pharmazie

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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.

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

Demopoulos

Tani

Long

1989

Archiv der Pharmazie

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Dopamine agonists: structure-activity relationships

Cannon

1985

Progress in Drug Research

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Neurochemical and behavioural profiles of five dopamine analogues

Sumners

Dijkstra

Vries

et al. 1981

Naunyn-Schmiedeberg's Arch. Pharmacol.

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The dopaminergic actions of five hydroxylated dopamine analogues have been examined for: i) Ability to induce stereotypy, ii) Effects upon dopamine metabolism, iii) Ability to antagonise the rise in striatal dopamine caused by gammabutyrolactone. With the exception of the resorcinol derivative 2-(3,5-dihydroxyphenyl)-N,N-dipropylethylamine, all of the compounds tested exhibited dopamine-like actions, and similarities were found in the induction of stereotypy and in the reduction of dopamine metabolism. For example, 2-(3-hydroxyphenyl)-N,N-dipropylethylamine had a short duration of action as far as reducing dopamine metabolism and inducing stereotypy were concerned. On the other hand, 2-(3-hydroxyphenyl)-N-n-propyl-N-phenyl-ethyl-ethylamine (e) and also 5-hydroxy-2-(N-n-propyl-N-phenylethyl)-aminotetralin had a long duration of agonist-like effects upon both parameters, the aminotetralin derivative being the more potent of the two. Thus, in going from the simple dopamine-like structure to the aminotetralin compound there has been an increase in dopamine agonist-like activity. The differences in dopamine agonist potency of the drugs used are discussed in relation to the structure of these compounds, and are compared with the potencies or related compounds. Also, the potencies of the compounds under investigation upon presynaptic dopamine receptors (using the gammabutyrolactone model as a test system) were investigated, and the ester, 2-(3-benzoyloxyphenyl)-N-n-propyl-N-phenylethyl-ethylamine was the most potent. This ester, which is probably converted to (e) in the brain, also had a long duration of action in the stereotypy and dopamine metabolism tests. The results suggest that certain of the compounds might be useful leads for the design of dopamine agonists of possible clinical use.

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Profil psychopharmacologique d'un nouvel agoniste Dopaminergique, le RU 24213

Cited by 10 publications

References 16 publications

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

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

Dopamine agonists: structure-activity relationships

Neurochemical and behavioural profiles of five dopamine analogues

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