Synthesis of Quinoline Derivatives as 5-HT4 Receptor Ligands

Amir Hanna-Elias; David T. Manallack; Isabelle Berque-Bestel; Helen R. Irving; Ian M. Coupar; Magdy N. Iskander

doi:10.1071/CH08505

RESEARCH ARTICLE

Synthesis of Quinoline Derivatives as 5-HT₄ Receptor Ligands

Amir Hanna-Elias ^A , David T. Manallack ^A , Isabelle Berque-Bestel ^B ^C , Helen R. Irving ^A , Ian M. Coupar ^A and Magdy N. Iskander ^A ^D

+ Author Affiliations

- Author Affiliations

^A Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia.

^B Inserm U869, Bordeaux, 33076, France.

^C Université Victor Segalen, Bordeaux 2, 33076, France.

^D Corresponding author. Email: magdy.iskander@pharm.monash.edu.au

Australian Journal of Chemistry 62(2) 150-156 https://doi.org/10.1071/CH08505
Submitted: 18 November 2008 Accepted: 9 January 2009 Published: 19 February 2009

Abstract

A general and convenient synthesis of 6-methoxyquinoline-3-carboxamides commencing with a cyclization step that involves ρ-anisidine and diethyl (ethoxymethylene)malonate is described. An additional tetrahydroquinoline scaffold 19 is prepared from 6-methoxyquinoline-3-carboxamide and this represents a novel serotinergic lead structure. These compounds show reasonable affinity at 1 × 10^–6 M, and docking experiments suggest that they may bind in a similar manner to serotonin.

^* Compounds 5, 6, 8, and 11 have been reported previously but without detailed structure identification. As such, they have been described in the experimental section.

Acknowledgements

The authors sincerely thank the Monash Institute of Pharmaceutical Sciences (Monash University) for providing a Ph.D. scholarship, and Dr S. Egan and Mr K. Chinkwo for their assistance. The mammalian expression vector pcDNA3.1/5-HT_4b was a gift from Dr F. O. Levy (University of Oslo).

References

Synthesis of Quinoline Derivatives as 5-HT4 Receptor Ligands

Abstract

Acknowledgements

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Synthesis of Quinoline Derivatives as 5-HT₄ Receptor Ligands