Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and related derivatives as dopamine receptors ligands.

doi:10.1021/JM960318V

Paper

Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and related derivatives as dopamine receptors ligands.

Published Oct 11, 1996 · F. Claudi, G. Cingolani, A. Di Stefano

Journal of medicinal chemistry

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10

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0

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Abstract

The present work reports the synthesis of enantiomeric pairs of the trans-2-amino-6-hydroxy-1-phenyl-2,3-dihydro-1H-indene [(+)-14a, (-)-14a] and trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1 H-indene [(+)-14b, (-)-14b] and their N,N-di-n-propyl [(+)-and (-)-15a,b], N-methyl-N-allyl [(+)-and (-)-16a,b], and N-methyl-N-n-propyl [(+) and (-)-17a,b] derivatives obtained by a combination of stereospecific reactions and optical resolution. The new compounds were evaluated for their affinity at the dopamine D1 and D2 receptors. The amines (+)- and (-)-14a, incorporating the D1 pharmacophore 2-phenyl-2-(3-hydroxyphenyl)ethylamine in a trans extended conformation, and their derivatives displayed D1 and D2 affinity in the nanomolar range. On the other hand, the enantiomers (+)- and (-)-14b, (+)- and (-)-15b displayed high affinity and selectivity for the D1 receptor. In a preliminary behavioral study on rats (+)-14b, and to a greater extent (+)-15b, promoted episodes of intense grooming, thus indicating that they act as central D1 agonists. The trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1H-indenes (+)-14b and (+)-15b represent selective D1 agonists lacking a catechol group, which should meet the prerequisites for a central nervous system penetration.

In Vitro Study

Study Snapshot

The trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes (+)-14b and (+)-15b show high affinity and selectivity for the D1 receptor, with potential for central nervous system penetration.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and related derivatives as dopamine receptors ligands.

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References

Citations

Intermolecular cascade annulations of N-(arylsulfonyl)acrylamides with dual C(sp3)-H bonds: divergent access to indanes and pyrrolidin-2-ones.

This study presents a new intermolecular cascade annulation reaction for producing indanes and pyrrolidin-2-ones, offering a new approach to synthesis of these compounds.

Dopamine D1 receptor ligands: Where are we now and where are we going

Dopamine D1 receptor agonists show promise for Parkinson's disease treatment, but their clinical trial results are not encouraging.

[6 + 3] Cycloaddition of Fischer aminocarbene complexes: An efficient annulation of fulvenes to indene derivatives

This study demonstrates a regioselective [6 + 3] cycloaddition of Fischer aminocarbene complexes to pentafulvenes, leading to dihydroindenes and indene derivatives, with potential applications in organic synthesis.

Incorporation of an indole-containing diarylbutylamine pharmacophore into furo[2,3-a]carbazole ring systems

The indole-containing diarylbutylamine pharmacophore can be incorporated into furo[2,3-a]carbazole ring systems through Hg2+-induced cyclisation of a carbazole alkynol.

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Intramolecular Ritter reactions of 2-(2-cyanoethyl)tetrahydrocyclopenta[b]indole and -carbazole derivatives can be used to construct various tetracyclic lactam compounds.