Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors.

Article Details

Citation

Copy to clipboard

Neves G, Menegatti R, Antonio CB, Grazziottin LR, Vieira RO, Rates SM, Noel F, Barreiro EJ, Fraga CA

Searching for multi-target antipsychotics: Discovery of orally active heterocyclic N-phenylpiperazine ligands of D2-like and 5-HT1A receptors.

Bioorg Med Chem. 2010 Mar 1;18(5):1925-35. doi: 10.1016/j.bmc.2010.01.040. Epub 2010 Jan 25.

PubMed ID

20153652 [ View in PubMed

]

Abstract

We described herein the design, synthesis, and pharmacological evaluation of N-phenylpiperazine heterocyclic derivatives as multi-target compounds potentially useful for the treatment of schizophrenia. The isosteric replacement of the heterocyclic ring at the biaryl motif generating pyrazole, 1,2,3-triazole, and 2-methylimidazole[1,2-a]pyridine derivatives resulted in 21 analogues with different substitutions at the para-biaryl and para-phenylpiperazine positions. Among the compounds prepared, 4 (LASSBio-579) and 10 (LASSBio-664) exhibited an adequate binding profile and a potential for schizophrenia positive symptoms treatment without cataleptogenic effects. Structural features of this molecular scaffold are discussed regarding binding affinity and selectivity for D(2)-like, 5-HT(1A), and 5-HT(2A) receptors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Bifeprunox	5-hydroxytryptamine receptor 1A	Ki (nM)	9.3	N/A	N/A	Details
Bifeprunox	Dopamine D2 receptor	Ki (nM)	2.2	N/A	N/A	Details