Synthesis of new serotonin 5-HT<inf>7</inf> receptor ligands. Determinants of 5-ht7/5-ht<inf>1a</inf> receptor selectivity

Rocío A. Medina; Jessica Sallander; Bellinda Benhamú; Esther Porras; Mercedes Campillo; Leonardo Pardo; María L. López-Rodríguez

doi:https://doi.org/10.1021/jm8014553

Synthesis of new serotonin 5-HT<inf>7</inf> receptor ligands. Determinants of 5-ht7/5-ht<inf>1a</inf> receptor selectivity

Rocío A. Medina, Jessica Sallander, Bellinda Benhamú, Esther Porras, Mercedes Campillo, Leonardo Pardo, María L. López-Rodríguez

Department of Paediatrics, Obstetrics and Gynaecology and Preventive Medicine and Public Health

Research output: Contribution to journal › Article › Research › peer-review

45 Citations (Scopus)

Abstract

We report the synthesis of a new set of compounds of general structure I (1-20) with structural modifications in the pharmacophoric elements of the previously reported lead UCM-5600. The new derivatives have been evaluated for binding affinity at 5-HT7 and 5-HT1A receptors. The influence of the different structural features in terms of 5-HT 7/5-HT1A receptor affinity and selectivity was analyzed by computational simulations of the complexes between compounds I and β2-based 3-D models of these receptors. Compound 18 (HYD 1) 1,3-dihydro-2H-indol-2-one; spacer) -(CH2)4-; HYD 2 + HYD3 3,4-dihydroisoquinolin-2(1 H)-yl) exhibits high 5-HT7R affinity (Ki) 7 nM) and selectivity over the 5-HT1AR (31-fold), and has been characterized as a partial agonist of the human 5-HT7R. © 2009 American Chemical Society.

Original language	English
Pages (from-to)	2384-2392
Journal	Journal of Medicinal Chemistry
Volume	52
DOIs	https://doi.org/10.1021/jm8014553
Publication status	Published - 23 Apr 2009

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Medina, R. A., Sallander, J., Benhamú, B., Porras, E., Campillo, M., Pardo, L., & López-Rodríguez, M. L. (2009). Synthesis of new serotonin 5-HT<inf>7</inf> receptor ligands. Determinants of 5-ht7/5-ht<inf>1a</inf> receptor selectivity. Journal of Medicinal Chemistry, 52, 2384-2392. https://doi.org/10.1021/jm8014553

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title = "Synthesis of new serotonin 5-HT7 receptor ligands. Determinants of 5-ht7/5-ht1a receptor selectivity",

abstract = "We report the synthesis of a new set of compounds of general structure I (1-20) with structural modifications in the pharmacophoric elements of the previously reported lead UCM-5600. The new derivatives have been evaluated for binding affinity at 5-HT7 and 5-HT1A receptors. The influence of the different structural features in terms of 5-HT 7/5-HT1A receptor affinity and selectivity was analyzed by computational simulations of the complexes between compounds I and β2-based 3-D models of these receptors. Compound 18 (HYD 1) 1,3-dihydro-2H-indol-2-one; spacer) -(CH2)4-; HYD 2 + HYD3 3,4-dihydroisoquinolin-2(1 H)-yl) exhibits high 5-HT7R affinity (Ki) 7 nM) and selectivity over the 5-HT1AR (31-fold), and has been characterized as a partial agonist of the human 5-HT7R. {\textcopyright} 2009 American Chemical Society.",

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Synthesis of new serotonin 5-HT<inf>7</inf> receptor ligands. Determinants of 5-ht7/5-ht<inf>1a</inf> receptor selectivity. / Medina, Rocío A.; Sallander, Jessica; Benhamú, Bellinda; Porras, Esther; Campillo, Mercedes ; Pardo, Leonardo; López-Rodríguez, María L.

In: Journal of Medicinal Chemistry, Vol. 52, 23.04.2009, p. 2384-2392.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Medina, Rocío A.

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AU - Campillo, Mercedes

AU - Pardo, Leonardo

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AB - We report the synthesis of a new set of compounds of general structure I (1-20) with structural modifications in the pharmacophoric elements of the previously reported lead UCM-5600. The new derivatives have been evaluated for binding affinity at 5-HT7 and 5-HT1A receptors. The influence of the different structural features in terms of 5-HT 7/5-HT1A receptor affinity and selectivity was analyzed by computational simulations of the complexes between compounds I and β2-based 3-D models of these receptors. Compound 18 (HYD 1) 1,3-dihydro-2H-indol-2-one; spacer) -(CH2)4-; HYD 2 + HYD3 3,4-dihydroisoquinolin-2(1 H)-yl) exhibits high 5-HT7R affinity (Ki) 7 nM) and selectivity over the 5-HT1AR (31-fold), and has been characterized as a partial agonist of the human 5-HT7R. © 2009 American Chemical Society.

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