2. Academic Validation
  3. Investigations on the 1-(2-biphenyl)piperazine motif: identification of new potent and selective ligands for the serotonin(7) (5-HT(7)) receptor with agonist or antagonist action in vitro or ex vivo

Investigations on the 1-(2-biphenyl)piperazine motif: identification of new potent and selective ligands for the serotonin(7) (5-HT(7)) receptor with agonist or antagonist action in vitro or ex vivo

  • J Med Chem. 2012 Jul 26;55(14):6375-80. doi: 10.1021/jm3003679.
Enza Lacivita 1,  Daniela Patarnello,  Nikolas Stroth,  Antonia Caroli,  Mauro Niso,  Marialessandra Contino,  Paola De Giorgio,  Pantaleo Di Pilato,  Nicola A Colabufo,  Francesco Berardi,  Roberto Perrone,  Per Svenningsson,  Peter B Hedlund,  Marcello Leopoldo
Affiliations

Affiliation

  • 1 Dipartimento Farmaco-Chimico, Università degli Studi di Bari A. Moro, via Orabona, 4, 70125, Bari, Italy.
PMID: 22738316 DOI: 10.1021/jm3003679
Abstract

Here we report the design, synthesis, and 5-HT(7) receptor affinity of a set of 1-(3-biphenyl)- and 1-(2-biphenyl)piperazines. The effect on 5-HT(7) affinity of various substituents on the second (distal) phenyl ring was analyzed. Several compounds showed 5-HT(7) affinities in the nanomolar range and >100-fold selectivity over 5-HT(1A) and adrenergic α(1) receptors. 1-[2-(4-Methoxyphenyl)phenyl]piperazine (9a) showed 5-HT(7) agonist properties in a guinea pig ileum assay but blocked 5-HT-mediated cAMP accumulation in 5-HT(7)-expressing HeLa cells.

Figures