Anticancer Activity and Mechanisms of Action of MAPK pathway inhibitors

13C NMR (125 MHz, CDCl3): C 20

13C NMR (125 MHz, CDCl3): C 20.76, 35.30, 36.67, 55.81, 64.68, 80.34, 88.06, 115.35, 120.42, 120.55, 125.37, 127.62, 128.07, 128.83, 128.89, 129.30, 130.18, 130.62, 131.65, 131.81, 133.40, 135.34, 137.46, 142.91, 154.39, 208.25; LC/MS(ESI): = 478 (M+); Anal. added to a solution of 4 (1 mmol) in 10 mL of dicholoromethane followed by trifluoroacetic acid (0.1 mmol). The reaction mixture was stirred overnight. After completion of the reaction, the stirred solution was washed with SL910102 water and dried over Na2SO4. The crude product obtained was purified by column chromatography with hexaneCethyl acetate (3:2 v/v) as eluent. Characterization Data for Spiro[acenaphthene-2.2-pyrrolidin]-1-one (5a) Pale yellow solid; 74% yield; mp 135C137C; IR (KBr) max 3,356, 1,711, 1,535, 1,352 cm?1; 1H NMR (500 MHz, CDCl3): H 1.87 (3H, s, N-CH3), 2.88 (1H, dd, = 14.5, 6.0 Hz, 6-CH2), 2.99 (1H, dd, = 14.5, 7.0 Hz, 6-CH2), 4.35C4.40 (1H, m, H-5), 4.62 (1H, d, = 11.0 Hz, H-3), 6.42 (1H, t, = 9.5 Hz, H-4), 6.75C6.91 (6H, m, ArH), 7.19 (2H, d, = 8.5 Hz, ArH), 7.52C7.58 (2H, m, SL910102 ArH), 7.79C7.98 (5H, m, ArH). 13C NMR (125 MHz, CDCl3): C 35.36, 36.69, 56.06, 64.71, 80.42, 87.72, 115.36, 120.41, 120.58, 125.45, 127.47, 127.73, 127.82, 128.08, 128.15, 128.84, 129.25, 130.17, 130.65, 131.82, 133.45, 135.34, 142.86, 154.39, 208.03; LC/MS(ESI): = 464 (M+); Anal. calcd for C29H24N2O4: C, 74.98; H, 5.21; N, 6.03%; found: C, 74.85; H, 5.32; N, 6.16%. Characterization Data for Spiro[acenaphthene-2.2-pyrrolidin]-1-one (5b) Pale yellow solid; 72% yield; mp 152C154C; IR (KBr) Rabbit polyclonal to PAK1 max 3,349, 1,713, 1,546, 1,358 cm?1; 1H NMR (500 MHz, CDCl3): H 1.85 (3H, s, N-CH3), 2.86 (1H, dd, = 14.5, 6.5 Hz, 6-CH2), 2.96 (1H, dd, = 14.5, 6.5 Hz, 6-CH2), 4.31C4.36 (1H, m, H-5), 4.55 (1H, d, = 11.0 Hz, H-3), 6.35 (1H, dd, = 10.0, 9.5 Hz, H-4), 6.68 (2H, d, = 9.0 Hz, ArH), 6.79 (2H, d, = 8.5 Hz, ArH), 7.01 (2H, d, = 8.5 Hz, ArH), 7.18 (2H, d, = 9.0 Hz, ArH), 7.56C7.62 (2H, m, Ar-H), 7.81C7.88 (3H, m, Ar-H), 8.01 (1H, d, = 7.5 Hz, ArH). 13C NMR (125 MHz, CDCl3): C 35.26, 36.63, 55.42, 64.52, 80.10, 87.63, 115.35, 120.53, 120.67, 125.64, 127.48, 128.30, 128.85, 129.15, 128.43, 130.23, 130.68, 131.08, 131.38, 132.08, 133.45, 135.33, 142.85, 154.37, 207.94; LC/MS(ESI): = 543 (M+); Anal. calcd for C29H23BrN2O4: C, 64.10; H, 4.27; N, 5.16%; found: C, 64.32; H, 4.11; N, 5.27%. Characterization Data for Spiro[acenaphthene-2.2-pyrrolidin]-1-one (5c) Pale yellow solid; 80% yield; mp 110C112C; IR (KBr) max 3,450, 1,712, 1,538, 1,355 cm?1; 1H NMR (500 MHz, CDCl3): H 1.86 (3H, s, N-CH3), 2.87 (1H, dd, = 14.5, 6.5 Hz, 6-CH2), 2.97 (1H, dd, = 14.5, 7.0 Hz, 6-CH2), 4.32C4.38 (1H, m, H-5), 4.58 (1H, d, = 10.5 Hz, H-3), 6.34C6.38 (1H, m, H-4), 6.74 (2H, d, = 8.5 Hz, ArH), 6.80 (2H, d, = 8.5 Hz, ArH), 6.85 (2H, d, = 8.5 Hz, ArH), 7.18 (2H, d, = 8.5 Hz, ArH), 7.55C7.58 (1H, m, ArH), 7.61 (1H, d, = 7.5 Hz, ArH), 7.80C7.88 (3H, m, ArH), 8.00 (1H, d, = 8.0 Hz, ArH). 13C NMR (125 MHz, CDCl3): C 35.27, 36.61, 55.38, 64.55, 80.20, 87.68, 115.38, 120.57, 120.67, 125.64, 127.47, 128.27, 128.41, 128.86, 129.02, 129.08, 130.21, 130.65, 132.11, 133.45, 133.79, 135.37, SL910102 142.84, 154.47, 208.08; LC/MS(ESI): = 498 (M+); Anal. calcd for C29H23ClN2O4: C, 69.81; H, 4.65; N, 5.61%; found: C, 69.65; H, 4.79; N, 5.50%. Characterization Data for Spiro[acenaphthene-2.2-pyrrolidin]-1-one (5d) Yellow solid; 75% yield; mp 123C125C; IR (KBr) max 3,542, 1,714, 1,537, 1,351 cm?1; 1H NMR (500 MHz, CDCl3): H 1.86 (3H, s, N-CH3), 2.02 (3H, s, CH3), 2.87 (1H, dd, = 14.0, 6.0 Hz, 6-CH2), 2.98 SL910102 (1H, dd, = 14.0, 7.5 Hz, 6-CH2), 4.32C4.38 (1H, m, H-5), 4.59 (1H, d, = 10.5 Hz, H-3), 6.39 (1H, t, = 9.5 Hz, H-4), 6.65C6.72 (4H, m, ArH), 6.80 SL910102 (2H, d, = 8.0 Hz, ArH), 7.19 (2H, d, = 8.5 Hz, ArH), 7.52C7.55 (1H, m, ArH), 7.59 (1H, d, = 6.5 Hz, ArH), 7.77C7.90 (3H, m, ArH), 7.97 (1H, d, = 8.0 Hz, ArH). 13C NMR (125 MHz, CDCl3): C 20.76, 35.30, 36.67, 55.81, 64.68, 80.34, 88.06, 115.35, 120.42, 120.55, 125.37, 127.62, 128.07, 128.83, 128.89, 129.30, 130.18, 130.62, 131.65, 131.81, 133.40, 135.34, 137.46, 142.91, 154.39, 208.25; LC/MS(ESI): = 478 (M+); Anal. calcd for C30H26N2O4: C, 75.30; H, 5.48; N, 5.85%; found: C, 75.48; H, 5.35; N, 5.74%..