, 2009). The rationale of the study may be summarized as follows: (a) the designed compounds fulfilled both non-classical opioid receptor pharmacophore models presented in Fig. 2 as well as the model for serotoninergic activity depicted in Fig. 3; (b) the designed series is aimed to determine

the effect of the second aromatic moiety on the antinociceptive activity; (c) the designed compounds were expected to have favorable values of lipohilicity and ADMET parameters for the activity in central nervous system; (d) the imidazo[1,2-a]pyrimidine ITF2357 nmr scaffold is present in many biologically active compounds which have been reported to exhibit not only central nervous system activity (Blackaby et al., 2006; Goodacre et al., 2006; Jensen et al., 2005; Matosiuk, et al., 1996; Tully et al., 1991) but also anti-inflammatory and analgesic (Abignente et al., 1994; Freeman et al., 1978; Sacchi et al., 1997; Vidal et al., 2001),

antibacterial (Al-Tel and Al-Qawasmeh, 2010; Moraski et al., 2012; Rival et al., 1992; Steenackers et al., 2011a, b), antiviral (Gueiffier et al., 1996), antifungal (Rival et al., 1991, 1993), insecticidal, acaricidal and nematocidal (Dehuri et al., 1983), hormonal (Sasaki et al., 2002), mutagenic (Turner et al., 1978), anticancer (Guo et al., 2011; Lin et al., 2012; Linton et al., 2011), and cardiovascular Caspase inhibitor review (Okabe et al., 1983) activity; (e) the set of substituents was similar to those in previously reported series (Fig. 1) which turned out to exhibit the expected profile of pharmacological activity. In this study, we present synthesis, computational drug-likeness estimation and ADMET pre-screening, pharmacological C1GALT1 activity determination, and some structure–activity relationship studies for the series of 24 1-aryl-6-benzyl-7-hydroxy-2,3-dihydroimidazo[1,2-a]pyrimidine-5(1H)-ones. The main finding of the studies is that although all the investigated compounds exhibited strong antinociceptive properties, this activity was not reversed by naloxone; thus, it is not mediated through opioid receptors. Materials and methods Chemistry Reactions were routinely

monitored by thin-layer chromatography (TLC) in silica gel (60 F254 Merck plates), and the products were visualized with ultraviolet light of 254 nm wavelength. All NMR spectra were acquired on Bruker Fourier 300 MHz spectrometer. Spectra were recorded at 25 °C using DMSO as a solvent with a non-spinning sample in 5 mm NMR-tubes. MS spectra were recorded on Bruker microTOF-Q II and processed using Compass Data Wnt inhibition analysis software. The elementary analysis was performed with the application of Perkin-Elmer analyzer. Melting points were determined with Boetius apparatus. General procedure to obtain compounds 3a–3x 0.02 mol of hydrobromide of 1-aryl-4,5-dihydro-1H-imidazol-2-amines (1a–1l), 0.02 mol of diethyl 2-benzylmalonate (2a), or diethyl 2-(2-chlorobenzyl)malonate (2b), 15 mL of 16.