Scheme 3 Synthesis of 3-4-[4-(2-metoxyphenyl)piperazin-1-yl]butyl3-azatricyclo[7.3.1.05,13]trideca-(12),5,7,9(13),10-pentaene-2,4-dione (20) All obtained compounds were purified by flash chromatography. Elemental analysis,

mass spectrometry, 1H NMR and 13C NMR spectra confirmed the identity of the products. For compounds 2 and 11, also for hydrochlorides of 6, 7, 19, BAY 73-4506 cell line and 20 X-ray analyses were done. Biology Cytotoxicity and anti HIV-1 activity Title compounds were tested in cell-based assay against the human immunodeficiency virus type-1 (HIV-1), using Efavirenz as reference inhibitor. The cytotoxicity was evaluated in parallel with the antiviral activity. None of tested compounds showed selective antiviral activity against HIV-1. However compounds 10 and 14 turned out cytotoxic for exponentially growing MT4 cells in the low micromolar range (CC50 = 9 μM) (Table 1). Table 1 Cytotoxicity and anti-HIV-1 activity of compounds selleck 3, 6–10, and 12–19 Compounds MT-4

HIV-1IIIB CC 50 a EC 50 b 3 90 >90 6 >100 >100 7 >100 >100 8 >100 >100 9 20 >20 10 9 >9 12 >100 >100 13 >100 >100 14 9 >9 15 >100 >100 16 >100 >100 17 >100 >100 18 >100 >100 19 >100 >100 Efavirenz 45 0.002 aCompound concentration (μM) required to reduce the viability of mock-infected MT-4 cells by 50 %, as determined by the MTT method bCompound concentration (μM) required to achieve 50 % protection of MT-4 cells from the HIV-1-induced cytopathogenicity, as determined by the MTT method X-ray structural analyses The crystal structures have been determined for three “phencyclone” derivatives

2, 6, and 7. Their main skeleton resembles buspirone, but have more bulky maleimide fragment and in the case of 2 there is no piperazine moiety (n-butyl chain is terminated by bromine atom). In structures 6 and 7, the aromatic fragment (p-chlorophenyl and o-fluorophenyl, respectively) is different from 2-pirymidinyl substituent in buspirone. In all of these structures phenanthrene moiety forms a kind of “roof” Bcl-w over n-butyl chain, and phenyl rings are situated like “wings” directed outside (Fig. 2). In structures 6 and 7, the piperazine moiety adopts chair conformation. All compounds crystallize in monoclinic system without solvent with one molecule in an asymmetric unit. Unit cell contains 4 molecules related by inversion center (Fig. 3). Fig. 2 Crystal structures of 2, 6, and 7. Thermal ellipsoids drawn at 50 % probability level Fig. 3 Crystal packing of 2, 6, and 7 The crystal structure of 2 is stabilized by two kinds of short interactions between C–H···O and C–H···Br (Fig. 4). In 6 there are three types of C–H···O contacts. The oxygen atom from maleimide moiety contacts with piperazine and phenanthrene fragments. Second one interacts with phenyl ring (Fig. 5).