title: Synthesis and in vitro binding studies of substituted piperidine naphthamides. Part II: Influence of the substitution on the benzyl moiety on the affinity for D2L, D4.2, and 5-HT2A receptors.
abstract: In continuation of our work on N-(piperidin-4-yl)-naphthamides, the effect of substituted benzyl groups on D(2L), D(4.2), and 5-HT(2A) receptor affinity was evaluated. In the 1-naphthamide series most compounds were highly selective for D(4.2) over D(2L) and 5-HT(2A) receptors. Halogen and methyl substitution in position 3 or 4 of the benzyl group increased D(4.2) affinity. In the 2-naphthamide series a similar high D(4.2) over D(2L) selectivity was retained while 5-HT(2A) affinity was increased. 3-Methoxy, 3-methyl, and 4-methyl substituents were favorable for D(4.2) affinity while halogens reduced affinity. 2-Naphthamides with a 3-bromo- or a 3-methyl group were mixed D(4.2)/5-HT(2A) ligands similar to their unsubstituted parent compound. All compounds from both series with significant affinity for D(4.2) and 5-HT(2A) receptors were antagonists.
authors.affiliation: Laboratoire de Chimie Thérapeutique, Université du Droit et de la Santé Lille II, rue du Professeur Laguesse 3, BP83, F-59006 Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Carato
authors.forename: Amaury
authors.initials: A
authors.lastname: Graulich
authors.forename: Niels
authors.initials: N
authors.lastname: Jensen
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Liégeois
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D009281:Naphthalenes / Q000138:chemical synthesis*; D010880:Piperidines / Q000138:chemical synthesis*; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050638:Receptors, Dopamine D4 / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D001593:Benzyl Compounds; D007202:Indicators and Reagents; D008024:Ligands; D009281:Naphthalenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4