1) bearing a new integrase www.selleckchem.com/products/isrib-trans-isomer.html recognition motif. The compound, 4-(5-(2,6-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-hydroxy-2-oxo-N-(2-oxopyrrolidin-1-yl)but-3-enamide,

exhibited significant antiviral activity against a diverse set of HIV isolates and an excellent profile with respect to human cytochrome P450 and uridine 5′-diphospho-glucuronosyltransferase isozymes. NMR spectra were recorded on a Varian Inova 500 MHz spectrometer. HRMS data were obtained using Q-TOF Ion Mobility mass spectrometer. UV spectra were recorded on a Varian Cary Model 3 spectrophotometer. 5-Bromo-2-methoxy-pyridine, synthetic reagents and solvents were purchased from Aldrich, St. Louis, MO. A concise methodology for the synthesis of compound 1 was developed that involved

8 steps and an overall yield of 25%. The key final step is described here. To a solution of 4-(5-(2,6-difluorobenzyl)-1-(2-fluorobenzyl)-2-oxo-1,2-dihydro-pyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid (1.2 g, 2.71 mmol), prepared using modifications of methodologies previously described by us (Seo et al., 2011), in dimethylformamide (15 mL) was added 1-hydroxybenzotriazole (0.55 g, 4.07 mmol), followed by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.57 g, 2.98 mmol) at 0 °C. The resulting mixture was stirred at 0 °C for 20 min and then 1-(amino)-2-pyrollidinone p-toluene sulfonate, (0.89 g, 3.25 mmol) and sodium bicarbonate (0.25 g, 2.98 mmol) were added. Stirring was continued for 2 h at 0–5 °C. After completion of the reaction, the reaction mixture Selleckchem BMS-734016 was quenched with water (50 mL). The resulting yellow solid was filtered and purified by trituration

sequentially with methanol followed by chloroform: pentane (1:1 v/v) to afford compound 1 (1.11 g, 78% yield), m.p. 175–176 °C. UV (methanol) λ 401 nm (ε 9,139), 318 nm Ixazomib in vivo (ε 6,225). 1H-NMR (CDCl3, 500 MHz): δ 15.2 (s,1H), 8.88 (s, 1H), 8.24 (s, 1H), 8.01 (s, 1H), 7.65 (s, 1H), 7.55 (t, 1H), 7.33–7.10 (m, 4H), 6.94 (t, 2H), 5.21 (s, 2H), 3.83 (s, 2H), 3.71 (t, 2H), 2.50 (t, 2H), 2.19 (m, 2H); 13C-NMR (CDCl3, 125 MHz): δ 181.2, 179.3, 173.4, 162.2, 162.1, 162.1, 160.2, 160.2, 160.1, 159.5, 159.0, 144.0, 141.7, 132.1, 132.0, 130.4, 130.4, 128.9, 128.8, 124.7, 124.8, 122.5, 122.4, 122.3, 116.6, 115.6, 115.4, 115.0, 111.7, 111.6, 111.5, 111.4, 98.5, 47.8, 47.4, 28.4, 24.3, 16.8. HRMS: calcd for C27H23F3N3O5 [M + H]+ 526.1590, found 526.1589. Compound purity was 99.6% (from HPLC data, which was supported by high-field 1H and 13C NMR spectral data and quantitative UV data). Molecular modeling of the crystal structure of prototype foamy virus (PFV) integrase intasome (PDB code 3OYA) with compound 1 docked within the catalytic site was achieved by using the Surflex-Dock package within Sybyl-X [Sybyl-X 1.3 (winnt_os5x) version] (Tripos, St.