The protein preparation procedure for flexible docking includes fixing the precise residues mainly, adding hydrogen atoms, removing irrelevant water molecules, adding charges, etc. (400 MHz, DMSO-= 5.3 Hz, 1H), 7.95 (d, = 8.7 Hz, 2H), 7.73 (s, 1H), 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 CGP 36742 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 CGP 36742 (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), CGP 36742 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 ITPKB (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 (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, 1H). HRMS (ESI): calcd for (C28H25Cl2N3O2S + H)+: CGP 36742 538.1123; discovered: 538.1199. (9l). Light yellowish solid, m.p. 221.2~222.0 C; 1H NMR (400.
