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Enhancing a CH-? Interaction to Increase the Affinity for 5-HT1A Receptors.

ABSTRACT: An electrostatic interaction related to a favorable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible reinforcement of this interaction to increase the affinity for 5-HT1A receptors, different 4-substituted-phenyl analogues were synthesized and tested. The most important increase of affinity is obtained with two electron-donating methyl groups in positions 3 and 5.

SUBMITTER: Liegeois JF

PROVIDER: S-EPMC4027751 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Enhancing a CH-π Interaction to Increase the Affinity for 5-HT1A Receptors.

Liégeois Jean-François JF Lespagnard Marc M Meneses Salas Elsa E Mangin Floriane F Scuvée-Moreau Jacqueline J Dilly Sébastien S

ACS medicinal chemistry letters 20140129 4

An electrostatic interaction related to a favorable position of the distal phenyl ring and a phenylalanine residue in the binding pocket would explain the higher 5-HT1A affinity of a 4-phenyl-1,2,3,6-tetrahydropyridine (THP) analogue compared to the corresponding 4-phenylpiperazine analogue. To explore a possible reinforcement of this interaction to increase the affinity for 5-HT1A receptors, different 4-substituted-phenyl analogues were synthesized and tested. The most important increase of aff ...[more]

PMID: 24900840

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