title: Synthesis and structural investigation of some pyrimido[5,4-c]quinolin-4(3H)-one derivatives with a long-chain arylpiperazine moiety as potent 5-HT(1A/2A) and 5-HT(7) receptor ligands.
abstract: A series of new pyrimido[5,4-c]quinolin-4(3H)-ones with variable length of the spacer between amide and 4-arylpiperazine moiety were prepared to further explore the role of a terminal portion in the serotonergic activity. The majority of compounds demonstrated high in vitro affinity for 5-HT(1A) receptor, and moderate-to-low affinity for 5-HT(2A) and 5-HT(7) receptors. X-ray analysis, two-dimensional NMR, conformational studies and docking into the 5-HT(1A) receptor model were conducted to investigate conformational preferences of selected 5-HT(1A) receptor ligands in different environments. The extended conformation of tetramethylene derivatives was found in a solid state, in DMSO (for a protonated form) and as a global energy minimum during conformational analysis in simulated water environment. Ligand geometry in top-scored complexes, obtained by docking to a set of 100 receptor models, were either fully extended or with central spacer torsion in synclinal conformation.
authors: Department of Hospital Pharmacy, Faculty of Pharmacy, Medical University of Lodz, 1 Muszynski Street, 91-151Lodz, Poland.
authors: Wieslawa
authors: W
authors: Lewgowd
authors: Andrzej J
authors: AJ
authors: Bojarski
authors: Malgorzata
authors: M
authors: Szczesio
authors: Andrzej
authors: A
authors: Olczak
authors: Marek L
authors: ML
authors: Glowka
authors: Stefan
authors: S
authors: Mordalski
authors: Andrzej
authors: A
authors: Stanczak