The potent compounds were selected as ligand examples, as well as the structures of PI3K (PDB code: 3TL5, http://www

The potent compounds were selected as ligand examples, as well as the structures of PI3K (PDB code: 3TL5, http://www.pdb.org/) were selected while the docking versions. (m, = 17.7, 11.6 Hz, 1H), 3.85 (s, 3H), 3.84C3.75 (m, 3H), 3.67 (s, 3H), 3.60C3.54 (m, 1H), 3.50C3.46 (m, 2H). HRMS (ESI): calcd for (C27H25N3OS + H)+: 440.1797; discovered: 440.1834. (9b). Light yellowish solid, m.p. 280C282 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.90 (dd, = 8.4, 5.5 Hz, 2H), 7.63 (dd, = 8.4, 5.0 Hz, 2H), 7.37 (dd, = 13.9, 7.0 Hz, 3H), 7.30C7.26 (m, 1H), 5.79 (dd, = 12.1, 6.1 Hz, 1H), 3.95 (dd, = 17.8, 12.2 Hz, 1H), 3.82C3.65 (m, 6H), 3.59 (d, = 7.7 Hz, 3H). HRMS (ESI): calcd for (C28H27N3O2S + H)+: 470.1902; discovered: 470.1946. (9c).Yellowish solid, m.p. 225C227 C; 1H NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 8.13 (s, 2H), 7.63 (s, 1H), 7.50C7.42 (m, 4H), 7.25 (t, = 8.5 Hz, 2H), 5.88 (s, 1H), 4.13 (d, = 12.1 Hz, 1H), 3.87 (s, 4H), 3.70 (s, 3H), 3.49 (s, 1H), 3.22 (s, 1H). HRMS (ESI): calcd for (C27H23F2N3OS + H)+: 476.1608; discovered: 476.1598. (9d).Yellowish solid, m.p. 286C289 C; 1H NMR (400 MHz, DMSO-= 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.49 (d, = 5.9 Hz, 1H). HRMS (ESI): calcd for (C28H26FN3O2S + H)+: 488.1808; discovered: 488.1853. (9e). Yellowish solid, m.p. 228.3~229.1 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.77 (d, = 7.1 Hz, 2H), 7.55 (d, = 8.4 Hz, 2H), 7.44 (d, = 7.6 Hz, 3H), 7.25 (d, = 5.5 Hz, 2H), 5.72 (dd, = 12.1, 5.7 Hz, 1H), 3.87 (dd, = 18.0, 12.3 Hz, 1H), 3.71 (s, 2H), 3.66C3.58 (m, 4H), 3.54 (s, 2H), 3.18 (dd, = 18.1, 5.8 Hz, 1H). HRMS (ESI): calcd for (C28H26BrN3Operating-system + H)+: 534.1041; discovered: 534.0991. (9f). Orange solid, m.p. 237.6~239.1 C; 1H NMR (400 MHz, DMSO-= 4.9 Hz, 1H), 7.79 (d, = 8.1 Hz, 2H), 7.35 (d, = 4.7 Hz, 1H), 7.29 (d, = 7.3 Hz, 2H), 7.24 (d, = 7.7 Hz, 3H), 7.03 (d, = 8.3 Hz, 2H), 5.69 (d, = 6.4 Hz, 1H), 3.98C3.87 (m, 2H), 3.80 (s, 3H), 3.68 (s, 4H), 3.57 (s, 4H). HRMS (ESI): calcd for (C27H23BrFN3Operating-system + H)+: 538.0790; discovered: 538.0882. (9g). Yellowish solid, m.p. 207.4~208.2 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.90 (d, = 7.6 Hz, 2H), 7.74 (s, 1H), 7.62 (dd, = 15.4, 6.7 Hz, 2H), 7.41C7.29 (m, 3H), 5.80 (dd, = 11.6, 6.2 Hz, 1H), 4.09 (dd, = 18.2, 11.5 Hz, 1H), 3.82 (s, 4H), 3.67 (s, 3H), 3.48 (s, 2H), 2.40 (s, 3H). HRMS (ESI): calcd for (C27H24BrN3Operating-system + H)+: 520.0884; discovered: 520.0865. (9h). Light yellowish solid, m.p. 222.8~223.9 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.73 (d, = 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.13 (d, = 13.7 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-calcd for (C27H23Cl2N3Operating-system + H)+: 508.1017; discovered: 508.1059. 4-(2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine (9i). Light yellowish solid, m.p. 231.7~233.2 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.77 (d, = 7.6 Hz, 2H), 7.48C7.37 (m, 3H), 7.30C7.17 (m, 6H), 5.71 (dd, = 12.0, 5.3 Hz, 1H), 3.87 (dd, = 17.4, 12.2 Hz, 1H), 3.63 (dt, = 19.1, 10.7 Hz, 6H), 3.49 (d, = 13.7 Hz, 2H), 3.45C3.40 (m, 1H). HRMS (ESI): calcd Rabbit polyclonal to Aquaporin2 for (C27H22Cl2FN3Operating-system + H)+: 528.0898; discovered: 528.0891. (9j). Light yellowish solid, m.p. 215.8~216.8 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.39C7.24 (m, 4H), 7.16 (t, = 8.8 Hz, 1H), 7.06 (d, = 8.6 Hz, 2H), 5.72 (dd, = 11.0, 5.3 Hz, 1H), 4.07C3.96 (m, 1H), 3.82 (s, 3H), 3.74 (s, 4H), 3.65C3.56 (m, 3H), 3.48 (s, 2H). HRMS (ESI): calcd for (C27H22BrCl2N3Operating-system + H)+: 588.0100; discovered: 588.0110. (9k). Yellowish solid, m.p. 221.2~222.0 C; 1H -NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 7.93C7.85 (m, 2H), 7.55 (d, = 8.2 Hz, 2H), 7.39C7.30 (m, 3H), 7.27 (d, = 8.3 Hz, 2H), 5.77 (dd, = 11.9, 5.4 Hz, 1H), 3.93 (dd, = 17.7, 12.3 Hz, 1H), 3.80C3.65 (m, 6H), 3.59 (d, = 10.2 Hz, 2H), 3.19 (dd, = 17.9, 5.8 Hz,.Cytotoxicity Assay In Vitro The cytotoxic activities of Substances 9aCl, 15aCl, and 21aCh were evaluated with A549, PC-3, HepG2, and MCF-7 cell lines by the typical MTT assay, with GDC-0941 like a positive control. 1H), 7.12 (d, = 8.4 Hz, 2H), 5.85C5.75 (m, 1H), 4.08 (m, = 17.7, 11.6 Hz, 1H), 3.85 (s, 3H), 3.84C3.75 (m, 3H), 3.67 (s, 3H), 3.60C3.54 (m, 1H), 3.50C3.46 (m, 2H). HRMS (ESI): calcd for (C27H25N3OS + H)+: 440.1797; discovered: 440.1834. (9b). Light yellowish solid, m.p. 280C282 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.90 (dd, = 8.4, 5.5 Hz, 2H), 7.63 (dd, = 8.4, 5.0 Hz, 2H), 7.37 (dd, = 13.9, 7.0 Hz, 3H), 7.30C7.26 (m, 1H), 5.79 (dd, = 12.1, 6.1 Hz, 1H), 3.95 (dd, = 17.8, 12.2 Hz, 1H), 3.82C3.65 (m, 6H), 3.59 (d, = 7.7 Hz, 3H). HRMS (ESI): calcd for (C28H27N3O2S + H)+: 470.1902; discovered: 470.1946. (9c).Yellowish solid, m.p. 225C227 C; 1H NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 8.13 (s, 2H), 7.63 (s, 1H), 7.50C7.42 (m, 4H), 7.25 (t, = 8.5 Hz, 2H), 5.88 (s, 1H), 4.13 (d, = 12.1 Hz, 1H), 3.87 (s, 4H), 3.70 (s, 3H), 3.49 (s, 1H), 3.22 (s, 1H). HRMS (ESI): calcd for (C27H23F2N3OS + H)+: 476.1608; discovered: 476.1598. (9d).Yellowish solid, m.p. 286C289 C; 1H NMR (400 MHz, DMSO-= 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = AN2728 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.49 (d, = 5.9 Hz, 1H). HRMS (ESI): calcd for (C28H26FN3O2S + H)+: 488.1808; discovered: 488.1853. (9e). Yellowish solid, m.p. 228.3~229.1 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.77 (d, = 7.1 Hz, 2H), 7.55 (d, = 8.4 Hz, 2H), 7.44 (d, = 7.6 Hz, 3H), 7.25 (d, = 5.5 Hz, 2H), 5.72 (dd, = 12.1, 5.7 Hz, 1H), 3.87 (dd, = 18.0, 12.3 Hz, 1H), 3.71 (s, 2H), 3.66C3.58 (m, 4H), 3.54 (s, 2H), 3.18 (dd, = 18.1, 5.8 Hz, 1H). HRMS (ESI): calcd for (C28H26BrN3Operating-system + H)+: 534.1041; discovered: 534.0991. (9f). Orange solid, m.p. 237.6~239.1 C; 1H NMR (400 MHz, DMSO-= 4.9 Hz, 1H), 7.79 (d, = 8.1 Hz, 2H), 7.35 (d, = 4.7 Hz, 1H), 7.29 (d, = 7.3 Hz, 2H), 7.24 (d, = 7.7 Hz, 3H), 7.03 (d, = 8.3 Hz, 2H), 5.69 (d, = 6.4 Hz, 1H), 3.98C3.87 (m, 2H), 3.80 (s, 3H), 3.68 (s, 4H), 3.57 (s, 4H). HRMS (ESI): calcd for (C27H23BrFN3Operating-system + H)+: 538.0790; discovered: 538.0882. (9g). Yellowish solid, m.p. 207.4~208.2 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.90 (d, = 7.6 Hz, 2H), 7.74 (s, 1H), 7.62 (dd, = 15.4, 6.7 Hz, 2H), 7.41C7.29 (m, 3H), 5.80 (dd, = 11.6, 6.2 Hz, 1H), 4.09 (dd, = 18.2, 11.5 Hz, 1H), 3.82 (s, 4H), 3.67 (s, 3H), 3.48 (s, 2H), 2.40 (s, 3H). HRMS (ESI): calcd for (C27H24BrN3Operating-system + H)+: 520.0884; discovered: 520.0865. (9h). Light yellowish solid, m.p. 222.8~223.9 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.73 (d, = 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.13 (d, = 13.7 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-calcd for (C27H23Cl2N3Operating-system + H)+: 508.1017; discovered: 508.1059. 4-(2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine (9i). Light yellowish solid, m.p. 231.7~233.2 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.77 (d, = 7.6 Hz, 2H), 7.48C7.37 (m, 3H), 7.30C7.17 (m, 6H), 5.71 (dd, = 12.0, 5.3 Hz, 1H), 3.87 (dd, = 17.4, 12.2 Hz, 1H), 3.63 (dt, = 19.1, 10.7 Hz, 6H), 3.49 (d, = 13.7 Hz, 2H), 3.45C3.40 (m, 1H). HRMS (ESI): calcd for (C27H22Cl2FN3Operating-system + H)+: 528.0898; discovered: 528.0891. (9j). Light yellowish solid, m.p..HRMS (ESI): calcd for (C27H24BrN3Operating-system + H)+: 517.0823; discovered: 517.0798. (15h). 7.62 (m, = 16.2, 7.0 Hz, 2H), 7.33 (d, = 8.1 Hz, 1H), 7.12 (d, = 8.4 Hz, 2H), 5.85C5.75 (m, 1H), 4.08 (m, = 17.7, 11.6 Hz, 1H), 3.85 (s, 3H), 3.84C3.75 (m, 3H), 3.67 (s, 3H), 3.60C3.54 (m, 1H), 3.50C3.46 (m, 2H). HRMS (ESI): calcd for (C27H25N3OS + H)+: 440.1797; discovered: 440.1834. (9b). Light yellowish solid, m.p. 280C282 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.90 (dd, = 8.4, 5.5 Hz, 2H), 7.63 (dd, = 8.4, 5.0 Hz, 2H), 7.37 (dd, = 13.9, 7.0 Hz, 3H), 7.30C7.26 (m, 1H), 5.79 (dd, = 12.1, 6.1 Hz, 1H), 3.95 (dd, = 17.8, 12.2 Hz, 1H), 3.82C3.65 (m, 6H), 3.59 (d, = 7.7 Hz, 3H). HRMS (ESI): calcd for (C28H27N3O2S + H)+: 470.1902; discovered: 470.1946. (9c).Yellowish solid, m.p. 225C227 C; 1H NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 8.13 (s, 2H), 7.63 (s, 1H), AN2728 7.50C7.42 (m, 4H), 7.25 (t, = 8.5 Hz, 2H), 5.88 (s, 1H), 4.13 (d, = 12.1 Hz, 1H), 3.87 (s, 4H), 3.70 (s, 3H), 3.49 (s, 1H), 3.22 (s, 1H). HRMS (ESI): calcd for (C27H23F2N3OS + H)+: 476.1608; discovered: 476.1598. (9d).Yellowish solid, m.p. 286C289 C; 1H NMR (400 MHz, DMSO-= 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.49 (d, = 5.9 Hz, 1H). HRMS (ESI): calcd for (C28H26FN3O2S + H)+: 488.1808; discovered: 488.1853. (9e). Yellowish solid, m.p. 228.3~229.1 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.77 (d, = 7.1 Hz, 2H), 7.55 (d, = 8.4 Hz, 2H), 7.44 (d, = 7.6 Hz, 3H), 7.25 (d, = 5.5 Hz, 2H), 5.72 (dd, = 12.1, 5.7 Hz, 1H), 3.87 (dd, = 18.0, 12.3 Hz, 1H), 3.71 (s, 2H), 3.66C3.58 (m, 4H), 3.54 (s, 2H), 3.18 (dd, = 18.1, 5.8 Hz, 1H). HRMS (ESI): calcd for (C28H26BrN3Operating-system + H)+: 534.1041; discovered: 534.0991. (9f). Orange solid, m.p. 237.6~239.1 C; 1H NMR (400 MHz, DMSO-= 4.9 Hz, 1H), 7.79 (d, = 8.1 Hz, 2H), 7.35 (d, = 4.7 Hz, 1H), 7.29 (d, = 7.3 Hz, 2H), 7.24 (d, = 7.7 Hz, 3H), 7.03 (d, = 8.3 Hz, 2H), 5.69 (d, = 6.4 Hz, 1H), 3.98C3.87 (m, 2H), 3.80 (s, 3H), 3.68 (s, 4H), 3.57 (s, 4H). HRMS (ESI): calcd for (C27H23BrFN3Operating-system + H)+: 538.0790; discovered: 538.0882. (9g). Yellowish solid, m.p. 207.4~208.2 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.90 (d, = 7.6 Hz, 2H), 7.74 (s, 1H), 7.62 (dd, = 15.4, 6.7 Hz, 2H), 7.41C7.29 (m, 3H), 5.80 (dd, = 11.6, 6.2 Hz, 1H), 4.09 (dd, = 18.2, 11.5 Hz, 1H), 3.82 (s, 4H), 3.67 (s, 3H), 3.48 (s, 2H), 2.40 (s, 3H). HRMS (ESI): calcd for (C27H24BrN3Operating-system + H)+: 520.0884; discovered: 520.0865. (9h). Light yellowish solid, m.p. 222.8~223.9 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.73 (d, = 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.13 (d, = 13.7 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-calcd for (C27H23Cl2N3Operating-system + H)+: 508.1017; discovered: 508.1059. 4-(2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine (9i). Light yellowish solid, m.p. 231.7~233.2 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.77 (d, = 7.6 Hz, 2H), 7.48C7.37 (m, 3H), 7.30C7.17 (m, 6H), 5.71 (dd, = 12.0, 5.3 Hz, 1H), 3.87 (dd, = 17.4, 12.2 Hz, 1H), 3.63 (dt, = 19.1, 10.7 Hz, 6H), 3.49 (d, = 13.7 Hz, 2H), 3.45C3.40 (m, 1H). HRMS (ESI): calcd for (C27H22Cl2FN3Operating-system + H)+: 528.0898; discovered: 528.0891. (9j). Light yellowish solid, m.p. 215.8~216.8 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.39C7.24 (m, 4H), 7.16 (t, = 8.8 Hz, 1H), 7.06 (d, = 8.6 Hz, 2H), 5.72 (dd, = 11.0, 5.3 Hz, 1H), 4.07C3.96 (m, 1H), 3.82 (s, 3H), 3.74 (s, 4H), 3.65C3.56 (m, 3H), 3.48 (s, 2H). HRMS (ESI): calcd for (C27H22BrCl2N3Operating-system + H)+: 588.0100; discovered: 588.0110. (9k). Yellowish solid, m.p. 221.2~222.0 C; 1H -NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 7.93C7.85 (m, 2H), 7.55 (d, = 8.2 Hz, 2H), 7.39C7.30.The formazan crystals were dissolved in 100 L of DMSO in each well, as well as the absorbency at 492 nm (for absorbance of MTT formazan) and 630 nm (for the reference wavelength) was measured with an enzyme linked immunosorbent assay (ELISA) reader (MR-96A Mindray Elisa Microplate Reader, Guangzhou, China). 1H), 3.50C3.46 (m, 2H). HRMS (ESI): calcd for (C27H25N3OS + H)+: 440.1797; discovered: 440.1834. (9b). Light yellowish solid, m.p. AN2728 280C282 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.90 (dd, = 8.4, 5.5 Hz, 2H), 7.63 (dd, = 8.4, 5.0 Hz, 2H), 7.37 (dd, = 13.9, 7.0 Hz, 3H), 7.30C7.26 (m, 1H), 5.79 (dd, = 12.1, 6.1 Hz, 1H), 3.95 (dd, = 17.8, 12.2 Hz, 1H), 3.82C3.65 (m, 6H), 3.59 (d, = 7.7 Hz, 3H). HRMS (ESI): calcd for (C28H27N3O2S + H)+: 470.1902; discovered: 470.1946. (9c).Yellowish solid, m.p. 225C227 C; 1H NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 8.13 (s, 2H), 7.63 (s, 1H), 7.50C7.42 (m, 4H), 7.25 (t, = 8.5 Hz, 2H), 5.88 (s, 1H), 4.13 (d, = 12.1 Hz, 1H), 3.87 (s, 4H), 3.70 (s, 3H), 3.49 (s, 1H), 3.22 (s, 1H). HRMS (ESI): calcd for (C27H23F2N3OS + H)+: 476.1608; discovered: 476.1598. (9d).Yellowish solid, m.p. 286C289 C; 1H NMR (400 MHz, DMSO-= 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.49 (d, = 5.9 Hz, 1H). HRMS (ESI): calcd for (C28H26FN3O2S + H)+: 488.1808; discovered: 488.1853. (9e). Yellowish solid, m.p. 228.3~229.1 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.77 (d, = 7.1 Hz, 2H), 7.55 (d, = 8.4 Hz, 2H), 7.44 (d, = 7.6 Hz, 3H), 7.25 (d, = 5.5 Hz, 2H), 5.72 (dd, = 12.1, 5.7 Hz, 1H), 3.87 (dd, = 18.0, 12.3 Hz, 1H), 3.71 (s, 2H), 3.66C3.58 (m, 4H), 3.54 (s, 2H), 3.18 (dd, = 18.1, 5.8 Hz, 1H). HRMS (ESI): calcd for (C28H26BrN3Operating-system + H)+: 534.1041; discovered: 534.0991. (9f). Orange solid, m.p. 237.6~239.1 C; 1H NMR (400 MHz, DMSO-= 4.9 Hz, 1H), 7.79 (d, = 8.1 Hz, 2H), 7.35 (d, = 4.7 Hz, 1H), 7.29 (d, = 7.3 Hz, 2H), 7.24 (d, = 7.7 Hz, 3H), 7.03 (d, = 8.3 Hz, 2H), 5.69 (d, = 6.4 Hz, 1H), 3.98C3.87 (m, 2H), 3.80 (s, 3H), 3.68 (s, 4H), 3.57 (s, 4H). HRMS (ESI): calcd for (C27H23BrFN3Operating-system + H)+: 538.0790; discovered: 538.0882. (9g). Yellowish solid, m.p. 207.4~208.2 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.90 (d, = 7.6 Hz, 2H), 7.74 (s, 1H), 7.62 (dd, = 15.4, 6.7 Hz, 2H), 7.41C7.29 (m, 3H), 5.80 (dd, = 11.6, 6.2 Hz, 1H), 4.09 (dd, = 18.2, 11.5 Hz, 1H), 3.82 (s, 4H), 3.67 (s, 3H), 3.48 (s, 2H), 2.40 (s, 3H). HRMS (ESI): calcd for (C27H24BrN3Operating-system + H)+: 520.0884; discovered: 520.0865. (9h). Light yellowish solid, m.p. 222.8~223.9 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.73 (d, = 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.13 (d, AN2728 = 13.7 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-calcd for (C27H23Cl2N3Operating-system + H)+: 508.1017; discovered: 508.1059. 4-(2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine (9i). Light yellowish solid, m.p. 231.7~233.2 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.77 (d, = 7.6 Hz, 2H), 7.48C7.37 (m, 3H), 7.30C7.17 (m,.HRMS (ESI): calcd for (C27H22Cl2FN3Operating-system + H)+: 526.0923; discovered: 526.0889. (15j). 4.08 (m, = 17.7, 11.6 Hz, 1H), 3.85 (s, 3H), 3.84C3.75 (m, 3H), 3.67 (s, 3H), 3.60C3.54 (m, 1H), 3.50C3.46 (m, 2H). HRMS (ESI): calcd for (C27H25N3OS + H)+: 440.1797; discovered: 440.1834. (9b). Light yellowish solid, m.p. 280C282 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.90 (dd, = 8.4, 5.5 Hz, 2H), 7.63 (dd, = 8.4, 5.0 Hz, 2H), 7.37 (dd, = 13.9, 7.0 Hz, 3H), 7.30C7.26 (m, 1H), 5.79 (dd, = 12.1, 6.1 Hz, 1H), 3.95 (dd, = 17.8, 12.2 Hz, 1H), 3.82C3.65 (m, 6H), 3.59 (d, = 7.7 Hz, 3H). HRMS (ESI): calcd for (C28H27N3O2S + H)+: 470.1902; discovered: 470.1946. (9c).Yellowish solid, m.p. 225C227 C; 1H NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 8.13 (s, 2H), 7.63 (s, 1H), 7.50C7.42 (m, 4H), 7.25 (t, = 8.5 Hz, 2H), 5.88 (s, 1H), 4.13 (d, = 12.1 Hz, 1H), 3.87 (s, 4H), 3.70 (s, 3H), 3.49 (s, 1H), 3.22 (s, 1H). HRMS (ESI): calcd for (C27H23F2N3OS + H)+: 476.1608; discovered: 476.1598. (9d).Yellowish solid, m.p. 286C289 C; 1H NMR (400 MHz, DMSO-= 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.49 (d, = 5.9 Hz, 1H). HRMS (ESI): calcd for (C28H26FN3O2S + H)+: 488.1808; discovered: 488.1853. (9e). Yellowish solid, m.p. 228.3~229.1 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.77 (d, = 7.1 Hz, 2H), 7.55 (d, = 8.4 Hz, 2H), 7.44 (d, = 7.6 Hz, 3H), 7.25 (d, = 5.5 Hz, 2H), 5.72 (dd, = 12.1, 5.7 Hz, 1H), 3.87 (dd, = 18.0, 12.3 Hz, 1H), 3.71 (s, 2H), 3.66C3.58 (m, 4H), 3.54 (s, 2H), 3.18 (dd, = 18.1, 5.8 Hz, 1H). HRMS (ESI): calcd for (C28H26BrN3Operating-system + H)+: 534.1041; discovered: 534.0991. (9f). Orange solid, m.p. 237.6~239.1 C; 1H NMR (400 MHz, DMSO-= 4.9 Hz, 1H), 7.79 (d, = 8.1 Hz, 2H), 7.35 (d, = 4.7 Hz, 1H), 7.29 (d, = 7.3 Hz, 2H), 7.24 (d, = 7.7 Hz, 3H), 7.03 (d, = 8.3 Hz, 2H), 5.69 (d, = 6.4 Hz, AN2728 1H), 3.98C3.87 (m, 2H), 3.80 (s, 3H), 3.68 (s, 4H), 3.57 (s, 4H). HRMS (ESI): calcd for (C27H23BrFN3Operating-system + H)+: 538.0790; discovered: 538.0882. (9g). Yellowish solid, m.p. 207.4~208.2 C; 1H NMR (400 MHz, DMSO-= 5.4 Hz, 1H), 7.90 (d, = 7.6 Hz, 2H), 7.74 (s, 1H), 7.62 (dd, = 15.4, 6.7 Hz, 2H), 7.41C7.29 (m, 3H), 5.80 (dd, = 11.6, 6.2 Hz, 1H), 4.09 (dd, = 18.2, 11.5 Hz, 1H), 3.82 (s, 4H), 3.67 (s, 3H), 3.48 (s, 2H), 2.40 (s, 3H). HRMS (ESI): calcd for (C27H24BrN3Operating-system + H)+: 520.0884; discovered: 520.0865. (9h). Light yellowish solid, m.p. 222.8~223.9 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.73 (d, = 7.5 Hz, 2H), 7.54 (d, = 7.9 Hz, 2H), 7.31 (d, = 6.6 Hz, 3H), 7.25 (d, = 7.8 Hz, 2H), 5.74 (d, = 6.6 Hz, 1H), 3.95C3.84 (m, 1H), 3.76C3.63 (m, 6H), 3.59 (s, 2H), 3.13 (d, = 13.7 Hz, 1H), 2.40 (s, 3H). 13C NMR (101 MHz, DMSO-calcd for (C27H23Cl2N3Operating-system + H)+: 508.1017; discovered: 508.1059. 4-(2-(3,5-diphenyl-4,5-dihydro-1H-pyrazol-1-yl)thieno[2,3-d]pyrimidin-4-yl)morpholine (9i). Light yellowish solid, m.p. 231.7~233.2 C; 1H NMR (400 MHz, DMSO-= 5.5 Hz, 1H), 7.77 (d, = 7.6 Hz, 2H), 7.48C7.37 (m, 3H), 7.30C7.17 (m, 6H), 5.71 (dd, = 12.0, 5.3 Hz, 1H), 3.87 (dd, = 17.4, 12.2 Hz, 1H), 3.63 (dt, = 19.1, 10.7 Hz, 6H), 3.49 (d, = 13.7 Hz, 2H), 3.45C3.40 (m, 1H). HRMS (ESI): calcd for (C27H22Cl2FN3Operating-system + H)+: 528.0898; discovered: 528.0891. (9j). Light yellowish solid, m.p. 215.8~216.8 C; 1H NMR (400 MHz, DMSO-= 5.0 Hz, 1H), 7.39C7.24 (m, 4H), 7.16 (t, = 8.8 Hz, 1H), 7.06 (d, = 8.6 Hz, 2H), 5.72 (dd, = 11.0, 5.3 Hz, 1H), 4.07C3.96 (m, 1H), 3.82 (s, 3H), 3.74 (s, 4H), 3.65C3.56 (m, 3H), 3.48 (s, 2H). HRMS (ESI): calcd for (C27H22BrCl2N3Operating-system + H)+: 588.0100; discovered: 588.0110. (9k). Yellowish solid, m.p. 221.2~222.0 C; 1H -NMR (400 MHz, DMSO-= 5.6 Hz, 1H), 7.93C7.85 (m, 2H), 7.55 (d, = 8.2 Hz, 2H), 7.39C7.30 (m, 3H), 7.27 (d, = 8.3 Hz, 2H), 5.77 (dd, = 11.9, 5.4 Hz, 1H), 3.93.