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Cpd.	m.p., ¹H NMR, ¹³C NMR, HRMS (ESI), HPLC
1g	m.p. 207.2-208.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.12 (s, 1H), 8.06 (d, J = 2.2 Hz, 2H), 7.85-7.78 (m, 1H), 7.73-7.62 (m, 3H), 7.55 (d, J = 6.5 Hz, 2H), 4.33 (s, 1H), 4.20 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂C_l2N₄O₄S [M-H]^- 448.988 3, found 448.987 1. Purity: 95.232% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.291 min)
2g	m.p. 208.4-209.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.15 (s, 1H), 8.12 (t, J = 2.1 Hz, 1H), 7.87 (dt, J = 8.5, 2.1 Hz, 1H), 7.69 (q, J = 4.8 Hz, 2H), 7.39-7.19 (m, 5H), 4.08 (s, 1H), 3.78 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₂S [M-H]^- 404.003 2, found 404.002 2. Purity: 96.196% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.716 min)
3g	m.p. 211.2-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.15 (s, 1H), 8.10 (dd, J = 5.7, 2.0 Hz, 1H), 7.85 (dt, J = 8.4, 2.1 Hz, 1H), 7.77-7.55 (m, 2H), 7.45-6.98 (m, 4H), 4.06 (s, 1H), 3.83 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 8, found 421.992 9. Purity: 96.067% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.168 min)
4g	m.p. 211.4-212.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.17 (s, 1H), 8.08 (d, J = 2.1 Hz, 1H), 7.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.50 (dd, J = 5.8, 3.5 Hz, 1H), 7.28 (dd, J = 5.9, 3.5 Hz, 2H), 6.91 (dd, J = 5.8, 3.6 Hz, 1H), 4.08 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₃N₃O₂S [M+H]⁺ 439.978 9, found 439.977 5. Purity: 95.934% by HPLC (ACN/0.1% TFA = 50%, t_R = 7.936 min)
5g	m.p. 202.2-203.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.78 (s, 1H), 8.07 (d, J = 2.1 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.70-7.58 (m, 3H), 7.35 (dd, J = 6.6, 1.6 Hz, 2H), 7.22 (ddd, J = 7.9, 6.3, 2.8 Hz, 1H), 3.92 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂BrCl₂N₃O₂S [M+H]⁺ 483.928 3, found 485.925 7. Purity: 96.165% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.566 min)
6g	m.p. 205.1-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 11.98 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.26-7.19 (m, 1H), 7.12 (tt, J = 8.0, 6.4 Hz, 2H), 6.78-6.70 (m, 1H), 3.94 (s, 2H), 2.32 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M+H]⁺ 420.033 5, found 420.033 4. Purity: 96.421% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.537 min)
7g	m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.23 (s, 1H), 8.10 (dd, J = 5.1, 2.0 Hz, 1H), 7.85 (dd, J = 8.4, 2.1 Hz, 1H), 7.68 (dd, J = 5.4, 3.5 Hz, 2H), 7.43-7.29 (m, 1H), 7.11-7.01 (m, 3H), 4.08 (s, 1H), 3.79 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 3. Purity: 95.916% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.146 min)
8g	m.p. 203.4-204.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.11 (s, 1H), 8.11 (t, J = 2.3 Hz, 1H), 7.86 (dt, J = 8.5, 2.0 Hz, 1H), 7.73-7.62 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.03 (d, J = 7.7 Hz, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 9. Purity: 96.235% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.579 min)
9g	m.p. 213.2-214.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.22 (s, 1H), 8.11 (dd, J = 4.3, 2.0 Hz, 1H), 7.90-7.76 (m, 3H), 7.68 (d, J = 8.5 Hz, 2H), 7.53-7.40 (m, 2H), 4.12 (s, 1H), 3.83 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 169.30, 167.75, 165.99, 164.93, 140.05, 137.23, 135.40, 133.99, 133.45, 132.02, 131.45, 130.41, 129.59, 129.34, 127.94, 127.76, 126.09, 108.62, 31.36. HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 97.124% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.825 min)
10g	m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.87 (s, 1H), 12.25 (s, 1H), 8.10 (dd, J = 7.3, 2.1 Hz, 1H), 7.85 (dt, J = 8.7, 2.3 Hz, 1H), 7.60 (ddt, J = 24.7, 16.6, 8.6 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.989 5. Purity: 96.267% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.312 min)
11g	m.p. 205.2-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.41 (s, 1H), 8.21-8.07 (m, 3H), 7.86 (ddd, J = 8.6, 3.9, 2.0 Hz, 1H), 7.77-7.60 (m, 4H), 4.21 (s, 1H), 3.95 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 3, found 448.986 9. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.876 min)
12g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.27 (s, 1H), 8.11 (dd, J = 5.4, 2.0 Hz, 1H), 7.89-7.79 (m, 3H), 7.74-7.53 (m, 4H), 4.18 (s, 1H), 3.92 (s, 1H), 3.22 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₄S₂ [M+Na]⁺ 505.977 3, found 505.978 5. Purity: 96.952% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.268 min)
13g	m.p. 206.3-207.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.17 (s, 1H), 12.15 (s, 1H), 8.12 (dd, J = 5.2, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.33-7.22 (m, 2H), 7.22-7.10 (m, 2H), 4.05 (s, 1H), 3.77 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 5. Purity: 95.194% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.346 min)
14g	m.p. 205.1-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.09 (s, 1H), 8.10 (t, J = 1.9 Hz, 1H), 7.85 (dt, J = 8.5, 2.3 Hz, 1H), 7.67 (q, J = 4.6 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1H), 7.07-6.95 (m, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (d, J = 2.7 Hz, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 7. Purity: 95.268% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.826 min)
15g	m.p. 204.2-205.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.85 (s, 1H), 12.18 (s, 1H), 8.10 (dd, J = 5.3, 2.0 Hz, 1H), 7.94-7.77 (m, 3H), 7.72-7.59 (m, 2H), 7.34 (dd, J = 14.7, 8.0 Hz, 2H), 4.13 (s, 1H), 3.82 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 95.051% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.118 min)
16g	m.p. 207.4-208.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.07 (s, 1H), 8.11 (dd, J = 3.6, 2.0 Hz, 1H), 7.86 (dt, J = 8.4, 1.5 Hz, 1H), 7.73-7.62 (m, 2H), 7.15 (dd, J = 8.7, 1.8 Hz, 2H), 6.87 (dd, J = 8.7, 1.3 Hz, 2H), 3.98 (s, 1H), 3.70 (t, J = 4.7 Hz, 4H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₃S [M-H]^- 434.013 8, found 434.012 3. Purity: 96.271% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.261 min)
17g	m.p. 206.0-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.74 (s, 1H), 12.06 (s, 1H), 9.29 (d, J = 11.5 Hz, 1H), 8.12 (dd, J = 4.6, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.04 (dd, J = 8.6, 2.9 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 3.94 (s, 1H), 3.64 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₃S [M-H]^- 419.998 2, found 419.997 2. Purity: 97.629% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.561 min)
18g	m.p. 206.5-207.9 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.97 (s, 1H), 8.11 (t, J = 2.2 Hz, 1H), 7.86 (dt, J = 8.4, 1.9 Hz, 1H), 7.68 (dd, J = 7.6, 4.4 Hz, 2H), 6.99 (dd, J = 10.2, 8.0 Hz, 2H), 6.68 (dd, J = 13.7, 8.0 Hz, 2H), 3.90 (s, 1H), 3.63 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₄Cl₂N₄O₂S [M-H]^- 419.014 2, found 419.013 4. Purity: 95.081% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.146 min)
19g	m.p. 204.3-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.30 (s, 1H), 8.22 (dq, J = 8.8, 2.4 Hz, 2H), 8.11 (dd, J = 7.1, 2.0 Hz, 1H), 7.86 (dd, J = 8.4, 2.0 Hz, 1H), 7.74-7.60 (m, 2H), 7.52 (dd, J = 16.1, 8.7 Hz, 2H), 4.22 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 4, found 448.986 6. Purity: 95.967% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.591 min)
20g	m.p. 207.9-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.12 (s, 1H), 12.26 (s, 1H), 8.12 (t, J = 2.4 Hz, 1H), 7.87 (dt, J = 8.5, 1.8 Hz, 1H), 7.70 (dt, J = 8.3, 4.8 Hz, 4H), 7.47 (dd, J = 14.6, 7.9 Hz, 2H), 4.17 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.988 7. Purity: 95.181% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.173 min)
21g	m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 8.60- 8.45 (m, 2H), 8.11 (dd, J = 8.1, 2.0 Hz, 1H), 7.90-7.78 (m, 2H), 7.73-7.62 (m, 2H), 7.45 (ddd, J = 24.7, 8.0, 5.0 Hz, 1H), 4.10 (s, 1H), 3.86 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.998 2. Purity: 95.845% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.491 min)
22g	m.p. 208.3-209.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.997 1. Purity: 95.324% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.249 min)
23g	m.p. 204.1-205.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.11 (s, 1H), 8.00 (dd, J = 5.6, 2.0 Hz, 1H), 7.75 (dt, J = 8.4, 2.3 Hz, 1H), 7.64-7.53 (m, 2H), 7.32-7.16 (m, 1H), 7.14-6.65 (m, 2H), 4.00 (s, 1H), 3.80 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₁Cl₂F₂N₃O₂S [M+H]⁺ 441.999 0, found 441.999 2. Purity: 95.948% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.149 min)
24g	m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.996 4, found 491.9960. Purity: 95.945% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.159 min)
25g	m.p. 209.2-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 8.10 (dd, J = 7.4, 2.1 Hz, 1H), 7.88-7.62 (m, 4H), 7.60-7.50 (m, 1H), 7.25 (dt, J = 9.0, 7.6 Hz, 1H), 4.08 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 9, found 467.998 0. Purity: 95.461% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.591 min)
26g	m.p. 210.4-211.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.54 (s, 1H), 12.29 (s, 1H), 8.16-8.02 (m, 1H), 7.83 (td, J = 8.0, 7.3, 2.0 Hz, 1H), 7.78-7.59 (m, 3H), 7.58-7.37 (m, 2H), 4.12 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.995 8, found 491.996 4. Purity: 95.895% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.923 min)
27g	m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.04 (s, 1H), 12.86 (s, 1H), 8.08 (s, 1H), 7.96-7.79 (m, 3H), 7.70-7.62 (m, 2H), 7.32 (t, J = 9.1 Hz, 1H), 4.08 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 2, found 468.000 1. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.150 min)
28g	m.p. 209.3-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.32 (s, 1H), 8.08 (dd, J = 13.7, 2.0 Hz, 1H), 8.00 (d, J = 5.3 Hz, 2H), 7.94 (s, 1H), 7.83 (td, J = 8.7, 2.0 Hz, 1H), 7.73-7.59 (m, 2H), 4.23 (s, 1H), 4.04 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₁Cl₂F₆N₃O₂S [M+H]⁺ 541.993 2, found 541.992 6. Purity: 95.591% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.257 min)
29g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.28 (s, 1H), 12.21 (s, 1H), 7.85 (dd, J = 7.7, 3.4 Hz, 2H), 7.65-7.49 (m, 4H), 7.47-7.28 (m, 4H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₂S [M+H]⁺ 406.083 8, found 406.082 8. Purity: 96.219% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.824 min)
30g	m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.26 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.65-7.49 (m, 4H), 7.43-7.19 (m, 4H), 4.16 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.075 0. Purity: 95.193% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.781 min)
31g	m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.24 (s, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.64-7.48 (m, 5H), 7.46-7.31 (m, 3H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.044 0. Purity: 95.691% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.245 min)
32g	m.p. 203.3-204.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.14 (s, 1H), 8.58 (d, J = 4.8 Hz, 1H), 7.89 (dt, J = 14.8, 7.9 Hz, 2H), 7.69-7.48 (m, 5H), 7.34 (t, J = 5.9 Hz, 1H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.078 1. Purity: 95.015% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.228 min)
33g	m.p. 204.1-205.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 12.38 (s, 1H), 10.84 (s, 1H), 7.84 (td, J = 7.8, 1.7 Hz, 1H), 7.67-7.46 (m, 5H), 7.21-7.10 (m, 1H), 6.95-6.80 (m, 2H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 5. Purity: 95.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.629 min)
34g	m.p. 202.1-203.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.33 (s, 1H), 7.89 (s, 2H), 7.52 (d, J = 46.5 Hz, 5H), 7.24 (s, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 5. Purity: 96.018% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.104 min)
35g	m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.23 (s, 1H), 12.30 (s, 1H), 7.92-7.82 (m, 2H), 7.65-7.39 (m, 7H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 8. Purity: 95.771% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.263 min)
36g	m.p. 206.4-207.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.91 (s, 1H), 9.24 (d, J = 4.9 Hz, 1H), 8.51 (s, 3H), 8.21 (dd, J = 12.8, 4.0 Hz, 5H), 4.77 (s, 1H), 4.50 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.079 2. Purity: 95.142% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.813 min)
37g	m.p. 207.2-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.54 (s, 1H), 9.59 (s, 1H), 7.70-7.46 (m, 7H), 7.15 (s, 1H), 6.83-6.74 (m, 2H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.081 6. Purity: 95.177% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.183 min)
38g	m.p. 205.1-206.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.31 (s, 2H), 9.76 (s, 1H), 8.24-7.83 (m, 8H), 7.72-7.48 (m, 1H), 4.32 (s, 2H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.072 5. Purity: 95.834% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.102 min)
39g	m.p. 209.2-210.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.38 (s, 1H), 9.74 (s, 1H), 8.23 (s, 1H), 8.01-7.95 (m, 1H), 7.92-7.84 (m, 2H), 7.59 (d, J = 4.8 Hz, 2H), 7.16-7.07 (m, 2H), 6.51 (s, 1H), 4.26 (s, 2H), 3.85 (s, 3H). HRMS (ESI): calcd. for C₂₀H₁₆F₃N₃O₃S [M+H]⁺ 436.094 3, found 436.0933 7. Purity: 97.361% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.445 min)
40g	m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.32 (s, 1H), 8.28 (t, J = 8.8 Hz, 2H), 8.12 (d, J = 8.5 Hz, 2H), 7.85 (d, J = 4.9 Hz, 1H), 7.57 (ddd, J = 20.1, 11.3, 4.7 Hz, 4H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₃N₄O₄S [M+H]⁺ 451.068 9, found 451.068 1. Purity: 95.184% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.739 min)
41g	m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.25 (s, 1H), 8.08-8.00 (m, 2H), 7.87 (dd, J = 8.3, 5.2 Hz, 2H), 7.76 (d, J = 6.4 Hz, 1H), 7.65-7.46 (m, 4H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₃F₃N₄O₂S [M+H]⁺ 431.079 0, found 431.078 7. Purity: 96.226% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.816 min)
42g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 12.29 (s, 1H), 7.76-7.65 (m, 1H), 7.66-7.54 (m, 5H), 7.53-7.38 (m, 2H), 7.16 (dt, J = 9.9, 5.0 Hz, 1H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 8. Purity: 95.988% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.502 min)
43g	m.p. 207.2-208.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.08 (s, 1H), 12.32 (s, 1H), 7.95-7.84 (m, 2H), 7.64-7.47 (m, 4H), 7.43 (d, J = 3.4 Hz, 1H), 7.31-7.17 (m, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 9. Purity: 96.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.436 min)
44g	m.p. 211.2-212.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 9.08 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.1 Hz, 1H), 7.68-7.46 (m, 6H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.077 6. Purity: 95.901% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.195 min)
45g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.24 (s, 1H), 9.51 (s, 1H), 7.65-7.46 (m, 4H), 7.36 (s, 1H), 7.30-7.13 (m, 3H), 6.72 (d, J = 7.9 Hz, 1H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 9. Purity: 95.292% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.026 min)
46g	m.p. 205.2-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.43 (s, 1H), 13.09 (s, 1H), 12.29 (s, 1H), 8.55-8.37 (m, 1H), 8.27-8.07 (m, 1H), 8.00-7.84 (m, 1H), 7.56 (dtd, J = 12.4, 9.0, 7.8, 3.9 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.073 2. Purity: 95.723% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.273 min)
47g	m.p. 204.4-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.21 (s, 1H), 10.04 (d, J = 3.7 Hz, 1H), 7.66-7.43 (m, 6H), 7.29 (d, J = 4.9 Hz, 1H), 6.96 (td, J = 8.8, 4.0 Hz, 1H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 1. Purity: 95.519% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.523 min)
48g	m.p. 203.1-204.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.93 (s, 1H), 12.22 (s, 1H), 10.37 (s, 1H), 7.82 (dd, J = 8.2, 2.2 Hz, 1H), 7.68-7.46 (m, 5H), 7.32 (s, 1H), 6.99 (dd, J = 8.5, 2.9 Hz, 1H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.786% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.076 min)
49g	m.p. 207.3-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.25 (s, 1H), 10.11 (s, 1H), 7.79 (td, J = 9.1, 4.3 Hz, 1H), 7.64-7.43 (m, 4H), 7.10 (dd, J = 4.8, 2.4 Hz, 1H), 6.66 (dtt, J = 11.4, 4.1, 2.4 Hz, 2H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 2. Purity: 95.912% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.519 min)
50g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.75 (s, 1H), 12.23 (s, 1H), 10.09 (s, 1H), 7.69-7.46 (m, 5H), 7.23 (s, 1H), 6.89 (t, J = 2.4 Hz, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 4.13 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.529% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.157 min)
51g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.42 (s, 1H), 11.98 (s, 1H), 7.55 (ddd, J = 20.7, 7.9, 4.3 Hz, 6H), 6.98 (s, 1H), 6.59 (d, J = 8.3 Hz, 2H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₅F₃N₄O₂S [M+H]⁺ 421.094 7, found 421.093 9. Purity: 95.017% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.081 min)
52g	m.p. 205.4-206.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.61 (s, 1H), 7.76 (dd, J = 20.5, 7.8 Hz, 1H), 7.65-7.49 (m, 4H), 7.48-7.26 (m, 2H), 7.24-7.08 (m, 1H), 4.14 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂F₃N₃O₂S [M+H]⁺ 380.068 1, found 380.067 3. Purity: 95.196% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.537 min)

Cpd.	m.p., ¹H NMR, ¹³C NMR, HRMS (ESI), HPLC
1g	m.p. 207.2-208.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.12 (s, 1H), 8.06 (d, J = 2.2 Hz, 2H), 7.85-7.78 (m, 1H), 7.73-7.62 (m, 3H), 7.55 (d, J = 6.5 Hz, 2H), 4.33 (s, 1H), 4.20 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂C_l2N₄O₄S [M-H]^- 448.988 3, found 448.987 1. Purity: 95.232% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.291 min)
2g	m.p. 208.4-209.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.15 (s, 1H), 8.12 (t, J = 2.1 Hz, 1H), 7.87 (dt, J = 8.5, 2.1 Hz, 1H), 7.69 (q, J = 4.8 Hz, 2H), 7.39-7.19 (m, 5H), 4.08 (s, 1H), 3.78 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₂S [M-H]^- 404.003 2, found 404.002 2. Purity: 96.196% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.716 min)
3g	m.p. 211.2-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.15 (s, 1H), 8.10 (dd, J = 5.7, 2.0 Hz, 1H), 7.85 (dt, J = 8.4, 2.1 Hz, 1H), 7.77-7.55 (m, 2H), 7.45-6.98 (m, 4H), 4.06 (s, 1H), 3.83 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 8, found 421.992 9. Purity: 96.067% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.168 min)
4g	m.p. 211.4-212.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.17 (s, 1H), 8.08 (d, J = 2.1 Hz, 1H), 7.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.50 (dd, J = 5.8, 3.5 Hz, 1H), 7.28 (dd, J = 5.9, 3.5 Hz, 2H), 6.91 (dd, J = 5.8, 3.6 Hz, 1H), 4.08 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₃N₃O₂S [M+H]⁺ 439.978 9, found 439.977 5. Purity: 95.934% by HPLC (ACN/0.1% TFA = 50%, t_R = 7.936 min)
5g	m.p. 202.2-203.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.78 (s, 1H), 8.07 (d, J = 2.1 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.70-7.58 (m, 3H), 7.35 (dd, J = 6.6, 1.6 Hz, 2H), 7.22 (ddd, J = 7.9, 6.3, 2.8 Hz, 1H), 3.92 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂BrCl₂N₃O₂S [M+H]⁺ 483.928 3, found 485.925 7. Purity: 96.165% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.566 min)
6g	m.p. 205.1-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 11.98 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.26-7.19 (m, 1H), 7.12 (tt, J = 8.0, 6.4 Hz, 2H), 6.78-6.70 (m, 1H), 3.94 (s, 2H), 2.32 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M+H]⁺ 420.033 5, found 420.033 4. Purity: 96.421% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.537 min)
7g	m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.23 (s, 1H), 8.10 (dd, J = 5.1, 2.0 Hz, 1H), 7.85 (dd, J = 8.4, 2.1 Hz, 1H), 7.68 (dd, J = 5.4, 3.5 Hz, 2H), 7.43-7.29 (m, 1H), 7.11-7.01 (m, 3H), 4.08 (s, 1H), 3.79 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 3. Purity: 95.916% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.146 min)
8g	m.p. 203.4-204.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.11 (s, 1H), 8.11 (t, J = 2.3 Hz, 1H), 7.86 (dt, J = 8.5, 2.0 Hz, 1H), 7.73-7.62 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.03 (d, J = 7.7 Hz, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 9. Purity: 96.235% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.579 min)
9g	m.p. 213.2-214.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.22 (s, 1H), 8.11 (dd, J = 4.3, 2.0 Hz, 1H), 7.90-7.76 (m, 3H), 7.68 (d, J = 8.5 Hz, 2H), 7.53-7.40 (m, 2H), 4.12 (s, 1H), 3.83 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 169.30, 167.75, 165.99, 164.93, 140.05, 137.23, 135.40, 133.99, 133.45, 132.02, 131.45, 130.41, 129.59, 129.34, 127.94, 127.76, 126.09, 108.62, 31.36. HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 97.124% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.825 min)
10g	m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.87 (s, 1H), 12.25 (s, 1H), 8.10 (dd, J = 7.3, 2.1 Hz, 1H), 7.85 (dt, J = 8.7, 2.3 Hz, 1H), 7.60 (ddt, J = 24.7, 16.6, 8.6 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.989 5. Purity: 96.267% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.312 min)
11g	m.p. 205.2-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.41 (s, 1H), 8.21-8.07 (m, 3H), 7.86 (ddd, J = 8.6, 3.9, 2.0 Hz, 1H), 7.77-7.60 (m, 4H), 4.21 (s, 1H), 3.95 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 3, found 448.986 9. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.876 min)
12g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.27 (s, 1H), 8.11 (dd, J = 5.4, 2.0 Hz, 1H), 7.89-7.79 (m, 3H), 7.74-7.53 (m, 4H), 4.18 (s, 1H), 3.92 (s, 1H), 3.22 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₄S₂ [M+Na]⁺ 505.977 3, found 505.978 5. Purity: 96.952% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.268 min)
13g	m.p. 206.3-207.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.17 (s, 1H), 12.15 (s, 1H), 8.12 (dd, J = 5.2, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.33-7.22 (m, 2H), 7.22-7.10 (m, 2H), 4.05 (s, 1H), 3.77 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 5. Purity: 95.194% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.346 min)
14g	m.p. 205.1-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.09 (s, 1H), 8.10 (t, J = 1.9 Hz, 1H), 7.85 (dt, J = 8.5, 2.3 Hz, 1H), 7.67 (q, J = 4.6 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1H), 7.07-6.95 (m, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (d, J = 2.7 Hz, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 7. Purity: 95.268% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.826 min)
15g	m.p. 204.2-205.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.85 (s, 1H), 12.18 (s, 1H), 8.10 (dd, J = 5.3, 2.0 Hz, 1H), 7.94-7.77 (m, 3H), 7.72-7.59 (m, 2H), 7.34 (dd, J = 14.7, 8.0 Hz, 2H), 4.13 (s, 1H), 3.82 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 95.051% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.118 min)
16g	m.p. 207.4-208.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.07 (s, 1H), 8.11 (dd, J = 3.6, 2.0 Hz, 1H), 7.86 (dt, J = 8.4, 1.5 Hz, 1H), 7.73-7.62 (m, 2H), 7.15 (dd, J = 8.7, 1.8 Hz, 2H), 6.87 (dd, J = 8.7, 1.3 Hz, 2H), 3.98 (s, 1H), 3.70 (t, J = 4.7 Hz, 4H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₃S [M-H]^- 434.013 8, found 434.012 3. Purity: 96.271% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.261 min)
17g	m.p. 206.0-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.74 (s, 1H), 12.06 (s, 1H), 9.29 (d, J = 11.5 Hz, 1H), 8.12 (dd, J = 4.6, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.04 (dd, J = 8.6, 2.9 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 3.94 (s, 1H), 3.64 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₃S [M-H]^- 419.998 2, found 419.997 2. Purity: 97.629% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.561 min)
18g	m.p. 206.5-207.9 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.97 (s, 1H), 8.11 (t, J = 2.2 Hz, 1H), 7.86 (dt, J = 8.4, 1.9 Hz, 1H), 7.68 (dd, J = 7.6, 4.4 Hz, 2H), 6.99 (dd, J = 10.2, 8.0 Hz, 2H), 6.68 (dd, J = 13.7, 8.0 Hz, 2H), 3.90 (s, 1H), 3.63 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₄Cl₂N₄O₂S [M-H]^- 419.014 2, found 419.013 4. Purity: 95.081% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.146 min)
19g	m.p. 204.3-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.30 (s, 1H), 8.22 (dq, J = 8.8, 2.4 Hz, 2H), 8.11 (dd, J = 7.1, 2.0 Hz, 1H), 7.86 (dd, J = 8.4, 2.0 Hz, 1H), 7.74-7.60 (m, 2H), 7.52 (dd, J = 16.1, 8.7 Hz, 2H), 4.22 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 4, found 448.986 6. Purity: 95.967% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.591 min)
20g	m.p. 207.9-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.12 (s, 1H), 12.26 (s, 1H), 8.12 (t, J = 2.4 Hz, 1H), 7.87 (dt, J = 8.5, 1.8 Hz, 1H), 7.70 (dt, J = 8.3, 4.8 Hz, 4H), 7.47 (dd, J = 14.6, 7.9 Hz, 2H), 4.17 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.988 7. Purity: 95.181% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.173 min)
21g	m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 8.60- 8.45 (m, 2H), 8.11 (dd, J = 8.1, 2.0 Hz, 1H), 7.90-7.78 (m, 2H), 7.73-7.62 (m, 2H), 7.45 (ddd, J = 24.7, 8.0, 5.0 Hz, 1H), 4.10 (s, 1H), 3.86 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.998 2. Purity: 95.845% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.491 min)
22g	m.p. 208.3-209.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.997 1. Purity: 95.324% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.249 min)
23g	m.p. 204.1-205.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.11 (s, 1H), 8.00 (dd, J = 5.6, 2.0 Hz, 1H), 7.75 (dt, J = 8.4, 2.3 Hz, 1H), 7.64-7.53 (m, 2H), 7.32-7.16 (m, 1H), 7.14-6.65 (m, 2H), 4.00 (s, 1H), 3.80 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₁Cl₂F₂N₃O₂S [M+H]⁺ 441.999 0, found 441.999 2. Purity: 95.948% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.149 min)
24g	m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.996 4, found 491.9960. Purity: 95.945% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.159 min)
25g	m.p. 209.2-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 8.10 (dd, J = 7.4, 2.1 Hz, 1H), 7.88-7.62 (m, 4H), 7.60-7.50 (m, 1H), 7.25 (dt, J = 9.0, 7.6 Hz, 1H), 4.08 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 9, found 467.998 0. Purity: 95.461% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.591 min)
26g	m.p. 210.4-211.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.54 (s, 1H), 12.29 (s, 1H), 8.16-8.02 (m, 1H), 7.83 (td, J = 8.0, 7.3, 2.0 Hz, 1H), 7.78-7.59 (m, 3H), 7.58-7.37 (m, 2H), 4.12 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.995 8, found 491.996 4. Purity: 95.895% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.923 min)
27g	m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.04 (s, 1H), 12.86 (s, 1H), 8.08 (s, 1H), 7.96-7.79 (m, 3H), 7.70-7.62 (m, 2H), 7.32 (t, J = 9.1 Hz, 1H), 4.08 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 2, found 468.000 1. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.150 min)
28g	m.p. 209.3-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.32 (s, 1H), 8.08 (dd, J = 13.7, 2.0 Hz, 1H), 8.00 (d, J = 5.3 Hz, 2H), 7.94 (s, 1H), 7.83 (td, J = 8.7, 2.0 Hz, 1H), 7.73-7.59 (m, 2H), 4.23 (s, 1H), 4.04 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₁Cl₂F₆N₃O₂S [M+H]⁺ 541.993 2, found 541.992 6. Purity: 95.591% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.257 min)
29g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.28 (s, 1H), 12.21 (s, 1H), 7.85 (dd, J = 7.7, 3.4 Hz, 2H), 7.65-7.49 (m, 4H), 7.47-7.28 (m, 4H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₂S [M+H]⁺ 406.083 8, found 406.082 8. Purity: 96.219% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.824 min)
30g	m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.26 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.65-7.49 (m, 4H), 7.43-7.19 (m, 4H), 4.16 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.075 0. Purity: 95.193% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.781 min)
31g	m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.24 (s, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.64-7.48 (m, 5H), 7.46-7.31 (m, 3H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.044 0. Purity: 95.691% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.245 min)
32g	m.p. 203.3-204.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.14 (s, 1H), 8.58 (d, J = 4.8 Hz, 1H), 7.89 (dt, J = 14.8, 7.9 Hz, 2H), 7.69-7.48 (m, 5H), 7.34 (t, J = 5.9 Hz, 1H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.078 1. Purity: 95.015% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.228 min)
33g	m.p. 204.1-205.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 12.38 (s, 1H), 10.84 (s, 1H), 7.84 (td, J = 7.8, 1.7 Hz, 1H), 7.67-7.46 (m, 5H), 7.21-7.10 (m, 1H), 6.95-6.80 (m, 2H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 5. Purity: 95.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.629 min)
34g	m.p. 202.1-203.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.33 (s, 1H), 7.89 (s, 2H), 7.52 (d, J = 46.5 Hz, 5H), 7.24 (s, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 5. Purity: 96.018% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.104 min)
35g	m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.23 (s, 1H), 12.30 (s, 1H), 7.92-7.82 (m, 2H), 7.65-7.39 (m, 7H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 8. Purity: 95.771% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.263 min)
36g	m.p. 206.4-207.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.91 (s, 1H), 9.24 (d, J = 4.9 Hz, 1H), 8.51 (s, 3H), 8.21 (dd, J = 12.8, 4.0 Hz, 5H), 4.77 (s, 1H), 4.50 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.079 2. Purity: 95.142% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.813 min)
37g	m.p. 207.2-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.54 (s, 1H), 9.59 (s, 1H), 7.70-7.46 (m, 7H), 7.15 (s, 1H), 6.83-6.74 (m, 2H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.081 6. Purity: 95.177% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.183 min)
38g	m.p. 205.1-206.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.31 (s, 2H), 9.76 (s, 1H), 8.24-7.83 (m, 8H), 7.72-7.48 (m, 1H), 4.32 (s, 2H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.072 5. Purity: 95.834% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.102 min)
39g	m.p. 209.2-210.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.38 (s, 1H), 9.74 (s, 1H), 8.23 (s, 1H), 8.01-7.95 (m, 1H), 7.92-7.84 (m, 2H), 7.59 (d, J = 4.8 Hz, 2H), 7.16-7.07 (m, 2H), 6.51 (s, 1H), 4.26 (s, 2H), 3.85 (s, 3H). HRMS (ESI): calcd. for C₂₀H₁₆F₃N₃O₃S [M+H]⁺ 436.094 3, found 436.0933 7. Purity: 97.361% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.445 min)
40g	m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.32 (s, 1H), 8.28 (t, J = 8.8 Hz, 2H), 8.12 (d, J = 8.5 Hz, 2H), 7.85 (d, J = 4.9 Hz, 1H), 7.57 (ddd, J = 20.1, 11.3, 4.7 Hz, 4H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₃N₄O₄S [M+H]⁺ 451.068 9, found 451.068 1. Purity: 95.184% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.739 min)
41g	m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.25 (s, 1H), 8.08-8.00 (m, 2H), 7.87 (dd, J = 8.3, 5.2 Hz, 2H), 7.76 (d, J = 6.4 Hz, 1H), 7.65-7.46 (m, 4H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₃F₃N₄O₂S [M+H]⁺ 431.079 0, found 431.078 7. Purity: 96.226% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.816 min)
42g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 12.29 (s, 1H), 7.76-7.65 (m, 1H), 7.66-7.54 (m, 5H), 7.53-7.38 (m, 2H), 7.16 (dt, J = 9.9, 5.0 Hz, 1H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 8. Purity: 95.988% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.502 min)
43g	m.p. 207.2-208.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.08 (s, 1H), 12.32 (s, 1H), 7.95-7.84 (m, 2H), 7.64-7.47 (m, 4H), 7.43 (d, J = 3.4 Hz, 1H), 7.31-7.17 (m, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 9. Purity: 96.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.436 min)
44g	m.p. 211.2-212.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 9.08 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.1 Hz, 1H), 7.68-7.46 (m, 6H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.077 6. Purity: 95.901% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.195 min)
45g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.24 (s, 1H), 9.51 (s, 1H), 7.65-7.46 (m, 4H), 7.36 (s, 1H), 7.30-7.13 (m, 3H), 6.72 (d, J = 7.9 Hz, 1H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 9. Purity: 95.292% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.026 min)
46g	m.p. 205.2-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.43 (s, 1H), 13.09 (s, 1H), 12.29 (s, 1H), 8.55-8.37 (m, 1H), 8.27-8.07 (m, 1H), 8.00-7.84 (m, 1H), 7.56 (dtd, J = 12.4, 9.0, 7.8, 3.9 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.073 2. Purity: 95.723% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.273 min)
47g	m.p. 204.4-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.21 (s, 1H), 10.04 (d, J = 3.7 Hz, 1H), 7.66-7.43 (m, 6H), 7.29 (d, J = 4.9 Hz, 1H), 6.96 (td, J = 8.8, 4.0 Hz, 1H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 1. Purity: 95.519% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.523 min)
48g	m.p. 203.1-204.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.93 (s, 1H), 12.22 (s, 1H), 10.37 (s, 1H), 7.82 (dd, J = 8.2, 2.2 Hz, 1H), 7.68-7.46 (m, 5H), 7.32 (s, 1H), 6.99 (dd, J = 8.5, 2.9 Hz, 1H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.786% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.076 min)
49g	m.p. 207.3-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.25 (s, 1H), 10.11 (s, 1H), 7.79 (td, J = 9.1, 4.3 Hz, 1H), 7.64-7.43 (m, 4H), 7.10 (dd, J = 4.8, 2.4 Hz, 1H), 6.66 (dtt, J = 11.4, 4.1, 2.4 Hz, 2H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 2. Purity: 95.912% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.519 min)
50g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.75 (s, 1H), 12.23 (s, 1H), 10.09 (s, 1H), 7.69-7.46 (m, 5H), 7.23 (s, 1H), 6.89 (t, J = 2.4 Hz, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 4.13 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.529% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.157 min)
51g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.42 (s, 1H), 11.98 (s, 1H), 7.55 (ddd, J = 20.7, 7.9, 4.3 Hz, 6H), 6.98 (s, 1H), 6.59 (d, J = 8.3 Hz, 2H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₅F₃N₄O₂S [M+H]⁺ 421.094 7, found 421.093 9. Purity: 95.017% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.081 min)
52g	m.p. 205.4-206.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.61 (s, 1H), 7.76 (dd, J = 20.5, 7.8 Hz, 1H), 7.65-7.49 (m, 4H), 7.48-7.26 (m, 2H), 7.24-7.08 (m, 1H), 4.14 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂F₃N₃O₂S [M+H]⁺ 380.068 1, found 380.067 3. Purity: 95.196% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.537 min)


1g		23.06 ± 5.08	2g	11.35 ± 1.77
3g	7.53 ± 0.37	4g	10.48 ± 1.59
5g	45.40 ± 5.23	6g	17.03 ± 0.45
7g	10.48 ± 2.92	8g	8.01 ± 0.47
9g	0.97 ± 0.08	10g	6.81 ± 0.64
11g	7.17 ± 0.38	12g	10.48 ± 1.15
13g	11.35 ± 1.26	14g	13.62 ± 0.72
15g	3.24 ± 0.59	16g	17.03 ± 1.83
17g	17.03 ± 2.26	18g	27.24 ± 3.09
19g	8.01 ± 0.73	20g	11.35 ± 1.75
21g	13.26 ± 1.07	22g	9.73 ± 0.56
23g	12.38 ± 1.06	24g	6.75 ± 0.53
25g	1.70 ± 0.11	26g	6.49 ± 0.31
27g	5.24 ± 0.45	28g	6.49 ± 0.89


1g		23.06 ± 5.08	2g	11.35 ± 1.77
3g	7.53 ± 0.37	4g	10.48 ± 1.59
5g	45.40 ± 5.23	6g	17.03 ± 0.45
7g	10.48 ± 2.92	8g	8.01 ± 0.47
9g	0.97 ± 0.08	10g	6.81 ± 0.64
11g	7.17 ± 0.38	12g	10.48 ± 1.15
13g	11.35 ± 1.26	14g	13.62 ± 0.72
15g	3.24 ± 0.59	16g	17.03 ± 1.83
17g	17.03 ± 2.26	18g	27.24 ± 3.09
19g	8.01 ± 0.73	20g	11.35 ± 1.75
21g	13.26 ± 1.07	22g	9.73 ± 0.56
23g	12.38 ± 1.06	24g	6.75 ± 0.53
25g	1.70 ± 0.11	26g	6.49 ± 0.31
27g	5.24 ± 0.45	28g	6.49 ± 0.89


29g		9.88 ± 1.32	30g	7.12 ± 0.87
31g	5.82 ± 0.46	32g	26.35 ± 1.89
33g	15.21 ± 1.76	34g	7.08 ± 0.83
35g	10.19 ± 1.52	36g	> 100
37g	1.90 ± 0.21	38g	9.55 ± 1.23
39g	> 200	40g	6.77 ± 0.53
41g	14.55 ± 1.23	42g	7.07 ± 0.67
43g	8.77 ± 0.94	44g	28.93 ± 2.25
45g	9.61 ± 1.06	46g	4.81 ± 0.59
47g	1.33 ± 0.08	48g	4.36 ± 0.33
49g	5.81 ± 0.61	50g	9.45 ± 0.27
51g	4.48 ± 0.12	52g	1.41 ± 0.54


29g		9.88 ± 1.32	30g	7.12 ± 0.87
31g	5.82 ± 0.46	32g	26.35 ± 1.89
33g	15.21 ± 1.76	34g	7.08 ± 0.83
35g	10.19 ± 1.52	36g	> 100
37g	1.90 ± 0.21	38g	9.55 ± 1.23
39g	> 200	40g	6.77 ± 0.53
41g	14.55 ± 1.23	42g	7.07 ± 0.67
43g	8.77 ± 0.94	44g	28.93 ± 2.25
45g	9.61 ± 1.06	46g	4.81 ± 0.59
47g	1.33 ± 0.08	48g	4.36 ± 0.33
49g	5.81 ± 0.61	50g	9.45 ± 0.27
51g	4.48 ± 0.12	52g	1.41 ± 0.54

噻唑腙类IGF2BP2小分子抑制剂的设计、合成及生物活性研究

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张诗迪 ¹^,² , 马赛 ¹^,² , 王颖哲 ¹^,² , 蔡媛倩 ¹^,² , 张艳 ¹^,² , 尤启冬 ¹^,²^,^* , 郭小可 ¹^,²^,^*

药学学报 | 专题报道: 蛋白成熟与翻译后修饰的化学干预 2024,59(11): 3006-3016

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药学学报 | 专题报道: 蛋白成熟与翻译后修饰的化学干预 2024, 59(11): 3006-3016

噻唑腙类IGF2BP2小分子抑制剂的设计、合成及生物活性研究

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张诗迪¹^,², 马赛¹^,², 王颖哲¹^,², 蔡媛倩¹^,², 张艳¹^,², 尤启冬¹^,²^,^*, 郭小可¹^,²^,^*

作者信息

1.中国药科大学, 江苏省药物分子设计与成药性优化重点实验室, 江苏南京 210009

2.中国药科大学药学院, 江苏南京 210009

通讯作者:

^*尤启冬, E-mail: youqd@cpu.edu.cn;

郭小可, Tel: 13701475843, E-mail: kexin95@126.com

Design, synthesis and biological activity study of thiazolehydrazone-based small molecule inhibitors of IGF2BP2

Shi-di ZHANG¹^,², Sai MA¹^,², Ying-zhe WANG¹^,², Yuan-qian CAI¹^,², Yan ZHANG¹^,², Qi-dong YOU¹^,²^,^*, Xiao-ke GUO¹^,²^,^*

Affiliations

1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China

2. School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China

出版时间: 2024-11-12 doi: 10.16438/j.0513-4870.2024-0564

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摘要

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胰岛素样生长因子2 mRNA结合蛋白2 (insulin-like growth factor 2 mRNA binding protein 2, IGF2BP2) 是N⁶-甲基腺苷(N⁶-methyladenosine, m⁶A) 的识别蛋白, 介导了下游mRNA的稳定性, 是极具前景的抗肿瘤靶点。本研究基于课题组前期筛选的先导化合物1g, 以噻唑腙作为母核设计并合成了52个IGF2BP2小分子抑制剂, 其中9g、10g、37g、47g和52g等具有较好的靶标活性。该项工作是以噻唑腙为母核发展IGF2BP2小分子抑制剂的一次探索, 为后续相关研究奠定基础。

关键词

噻唑腙衍生物 / 胰岛素样生长因子2 mRNA结合蛋白2 / N⁶-甲基腺苷 / 小分子抑制剂 / 设计合成

Abstract

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Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is a recognition protein for N⁶-methyladenosine (m⁶A), mediating the stability of downstream mRNA, and is a promising anti-tumor target. Based on the lead compound 1g from previous screening, this study designed and synthesized 52 IGF2BP2 small molecule inhibitors using thiazole hydrazone as the parent nucleus. Among them, 9g, 10g, 37g, 47g and 52g showed good inhibitory activities. This work represents an initial exploration in the development of small molecule inhibitors targeting IGF2BP2, using thiazolehydrazone as the core structure. It lays a foundation for subsequent related research.

Key words

thiazole hydrazone derivative / insulin-like growth factor 2 mRNA binding protein 2 / N⁶-methyladenosine / small-molecule inhibitor / design and synthesis

引用本文

张诗迪, 马赛, 王颖哲, 蔡媛倩, 张艳, 尤启冬, 郭小可. 噻唑腙类IGF2BP2小分子抑制剂的设计、合成及生物活性研究. 药学学报, 2024 , 59 (11) : 3006 -3016 . DOI: 10.16438/j.0513-4870.2024-0564

Shi-di ZHANG, Sai MA, Ying-zhe WANG, Yuan-qian CAI, Yan ZHANG, Qi-dong YOU, Xiao-ke GUO. Design, synthesis and biological activity study of thiazolehydrazone-based small molecule inhibitors of IGF2BP2[J]. Acta Pharmaceutica Sinica, 2024 , 59 (11) : 3006 -3016 . DOI: 10.16438/j.0513-4870.2024-0564

正文

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表观遗传调控在细胞的生理过程中扮演着关键的作用^[1], 而表观遗传失调已被证明与多种疾病尤其是癌症密切相关^[2]。表观遗传学研究主要涉及到DNA、组蛋白和RNA的修饰^[3]。目前已确认了100余种的RNA转录后修饰, 而N⁶-甲基腺苷(N⁶-methyladenosine, m⁶A) 被认为是真核生物信使RNA (message RNA, mRNA) 中最丰富的修饰^{[4, 5]}。随着m⁶A甲基转移酶、去甲基酶和识别蛋白被逐步发现, 证明m⁶A修饰具有可逆性^[6]。其中m⁶A阅读蛋白(也被称为识别蛋白) 可通过调控RNA与蛋白之间的相互作用, 使m⁶A修饰的RNA发挥特定的生物学功能^[7]。这些阅读蛋白包括YTH结构域蛋白^[8]、核不均一核糖蛋白(heterogeneous nuclear ribonucleoprotein, hnRNP)^[9]、真核起始因子(eukaryotic translation initiation factor, eIF)^[10]和胰岛素样生长因子2 mRNA结合蛋白(insulin-like growth factor-2 mRNA-binding proteins, IGF2BPs) 等家族^{[11, 12]}。IGF2BPs是一类RNA结合蛋白, 其家族成员包括IGF2BP1、IGF2BP2和IGF2BP3, 它们主要通过结合、调控特定mRNA的稳定性和翻译过程来参与包括细胞增殖、存活、代谢以及肿瘤的发生与发展等在内的多种生物进程^[13] (图 1A)。

IGF2BP2作为IGF2BPs蛋白家族成员——一种新的m⁶A阅读蛋白, 可促进m⁶A修饰的mRNA的稳定及翻译^[13]。近年来多种研究证明, IGF2BP2可能诱导癌症的发生发展^[4]。靶向IGF2BP2具有潜在的治疗急性髓系白血病^[14]、肺腺癌^[15]、结直肠癌^[16]、胰腺癌^[17]及肝细胞癌^[18]的作用。随着对IGF2BP2蛋白结构及生理功能研究的深入, IGF2BP2已成为潜在的抗肿瘤药物靶标^[19]。目前暂无高活性、高选择性的靶向IGF2BP2小分子抑制剂的报道, 因此, 进一步开展关于靶向IGF2BP2小分子抑制剂的研究具有重要意义。

为寻找全新结构的IGF2BP2小分子抑制剂, 基于竞争性荧光偏振实验(fluorescence polarization assay, FP) 筛选商业化合物库和组内化合物库, 获得噻唑腙类化合物4EGI-1 (1g, 图 1B)^[20], 其对IGF2BP2与底物探针的结合显示出中等抑制活性(IC₅₀ = 23.06 ± 5.08 μmol·L^-1, 图 1C)。为了进一步提高活性并探索构效关系, 本研究以1g为先导化合物, 分别针对其A环(Ⅰ系列) 和B环(Ⅱ系列) 引入不同取代基(图 1B), 共获得目标化合物52个, 通过核磁共振氢谱(hydrogen nuclear magnetic resonance spectroscopy, ¹H NMR)、高分辨质谱(high resolution mass spectroscopy, HRMS) 确证其化学结构, 并通过高效液相色谱(high performance liquid chromatography, HPLC) 检测纯度。

结果与讨论

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1 化学合成

化合物1g~52g的合成如合成路线1所示。以商业购买的取代芳醛1a~28a为原料, 在乙酸钠的存在下, 与N-乙酰甘氨酸在醋酐中经Erlenmeyer-Plöchl反应^{[21, 22]}得到中间体1b~28b, 随后在浓盐酸条件下开环得到关键中间体1c~28c (合成路线1A)。同时, 以商业购买的取代芳酮1d~23d为原料, 醋酸作溶剂, 经液溴溴化得到中间体1e~23e, 然后与硫代氨基脲经Hantzsch反应^[23]得到关键中间体1f~23f (合成路线1B)。另将中间体13f经还原反应得到中间体24f (合成路线1C)。最后, 中间体1c~28c与中间体1f~24f或商业购买的25f在酸催化下进行缩合, 得到目标化合物1g~52g (合成路线1D、E), 理化常数及波谱数据见表 1。

2 生物活性测试

使用实验室表达并纯化的IGF2BP2蛋白对52个目标化合物进行了基于FP的活性测试。Ⅰ系列化合物相关结果如表 2所示, Ⅱ系列化合物相关结果如表 3所示。其中大部分化合物的半数抑制浓度(half maximal inhibitory concentration, IC₅₀) 在微摩尔级别, 特别是9g的活性(IC₅₀ = 0.97 ± 0.08 μmol·L^-1) 相较于1g (IC₅₀ = 23.06 ± 5.08 μmol·L^-1) 有较大的提高。

3 化合物的构效关系研究

基于化合物1g的结构, 将其拆分为两个部分: A环与B环, 分别进行优化, 以期得到活性更优的IGF2BP2小分子抑制剂。设计并合成了两个系列的噻唑腙类化合物, 共获得了28个A环改造衍生物(Ⅰ系列) 和24个B环改造衍生物(Ⅱ系列)。

3.1 Ⅰ系列化合物的构效关系研究

针对A环进行了一系列取代基的替换, 设计并合成化合物1g~18g。随后, 通过FP实验进行生物活性测试, 并对活性结果进行构效关系分析: ①从整体来看, A环带有吸电子基的化合物较带有给电子基的化合物活性更好, 带酸性基团的化合物较带碱性基团的化合物活性更好。②从各取代位置来看, A环邻位随着位阻的增大化合物的活性降低(如3g~6g); 间位酸性基团的引入有利于化合物活性的提高(如9g); 疏水基团会随着位阻的增大使化合物活性有所提高(如7g、8g和9g); 对位酸性基团的引入也能使得化合物活性有所提高, 而这种活性的提高没有间位取代明显(如15g)。这些发现为进一步的药物设计和优化提供了重要的指导。

在构效关系研究中, 发现硝基对小分子的抑制活性具有重要影响(如1g、11g和19g), 考虑到硝基基团潜在的毒性等不利影响, 采用生物电子等排策略进行了后续的结构优化。综合考虑取代基大小等因素后, 最终选择了吡啶基及邻二氟苯基对硝基苯进行替换, 设计合成了化合物21g~23g, 并通过FP实验对它们的靶标活性进行测试, 结果如表 2所示, 然而活性并没有明显改善。

基于上述构效关系分析的结果, 选择活性较好的两个化合物9g和10g进行分子对接研究, 预测它们与IGF2BP2蛋白可能的结合模式(图 2A、B)。对接结果显示, 9g可能与蛋白空腔内的碱性氨基酸Arg576形成离子键相互作用从而使活性提高(图 2A); 10g与空腔内的疏水氨基酸形成广泛的疏水作用可能使活性提高(图 2B)。

然后, 尝试对9g和10g进行改造, 以期进一步提高活性。考虑到对接结果显示9g和10g能够分别通过离子键和疏水作用与蛋白形成相互作用, 于是分别尝试增强这两种作用以提高活性: 针对离子键作用, 设想通过在酸性基团的邻位引入吸电子基团而使其酸性增强, 从而增强离子键的作用, 尝试在羧基邻位引入小位阻吸电子基团F原子, 以避免引入大位阻取代基而导致活性下降; 针对疏水作用, 考虑通过增加疏水基团的数量或者放大基团大小, 以增加分子与靶点蛋白的疏水相互作用。基于以上假设, 尝试引入三氟甲基, 以增强分子与靶标的相互作用(图 2C、D)。根据上述思路, 设计并合成了化合物23g~28g, 然而活性没有得到明显的改善。

3.2 Ⅱ系列化合物的构效关系研究

本阶段, 选择保留A环的三氟甲基对B环进行一系列取代基的替换。首先, 设计并合成了化合物29g~39g和42g~46g, 通过FP实验对它们的靶标活性进行测试, 活性结果如表 3所示, 并对构效关系进行分析: ① B环邻位引入小位阻疏水基团较亲水基团活性更好, 而吡啶基的引入导致化合物的活性大幅度下降(如29g~33g); ② B环间位引入取代基会使得活性有微弱的提升, 其基团优先顺序为酸性基团 > 疏水基团 > 碱性基团, 吡啶基的引入导致活性大幅下降(如42g~46g); ③ B环对位引入小位阻疏水基团对活性有微弱改善, 羟基的引入使得活性有明显提高(如34g~39g)。

鉴于B环对位的羟基取代对活性的重要贡献, 通过分子对接对37g与IGF2BP2蛋白的可能得结合模式进行分析, 寻找结合腔内可能与小分子形成重要相互作用的氨基酸(图 2E), 以期提高化合物的活性。分子对接结果显示, 37g中B环羟基的O原子可能与Gln489相互作用, O-H与Gln569相互作用; 另外还观察到, 噻唑环和苯环可能与一些氨基酸(如Arg573等) 产生阳离子-π堆叠作用, 基于上述假设, 接下来考虑从增强这两个方面的作用来尝试进一步提高活性。

于是设计并合成了化合物47g~50g及52g, ①对于氢键作用, 通过在羟基的邻位引入吸电子基, 以增加羟基的酸性, 从而增强其氢键供体的能力; 考虑到位阻效应, 选择在氢键邻位引入F原子, 设计合成化合物47g及一系列疏水基团对照; ②对阳离子-π堆叠作用, 尝试通过在小分子芳香环上引入额外的环状结构以扩大芳香环大小, 从而增强小分子与靶点之间的阳离子-π相互作用。将4-苯基噻唑环改为苯并噻唑环, 以29g作为对照设计合成了化合物52g。

FP实验结果显示, 在B环羟基的邻位或对位引入吸电子基, 活性提高(如47g较37g活性提高), 初步证实上述假设; 另外52g较29g活性明显提高, 表明该区域的阳离子-π堆叠作用对活性有重要影响。上述实验结果, 进一步验证了52g与IGF2BP2蛋白的分子对接结果(图 2F)。最后, 尝试通过生物电子等排策略对37g中B环的羟基进行替换, 进一步对结构进行优化来改善小分子的亲和力。选择了羟基的生物电子等排体(如氨基和氰基等), 设计合成化合物37g、40g、41g和51g, 并通过FP实验对它们的靶标活性进行测试。结果显示, 这些基团的引入并未能使活性改善。

4 结论

前期通过荧光偏振高通量筛选方法对组内的化合物库进行筛选, 获得了分子量较小且具有中等抑制活性的苗头化合物1g (IC₅₀ = 23.06 ± 5.08 μmol·L^-1)。在化合物1g的基础上, 通过分子对接对其结合模式进行分析, 并展开进一步的结构优化工作, 最终得到活性大幅提高的Ⅰ系列化合物9g (IC₅₀ = 0.97 ± 0.08 μmol·L^-1)、10g (IC₅₀ = 6.81 ± 0.64 μmol·L^-1) 和Ⅱ系列化合物47g (IC₅₀ = 1.33 ± 0.08 μmol·L^-1) 和52g (IC₅₀ = 1.41 ± 0.54 μmol·L^-1)。通过噻唑腙系列化合物的优化工作, 初步总结了构效关系, 为进一步开展噻唑腙类IGF2BP2小分子抑制剂研究提供了参考。

该项工作是以噻唑腙为母核发展IGF2BP2小分子抑制剂的一次探索, 相关活性化合物可以作为先导化合物进行进一步的结构优化, 以获得活性更高的IGF2BP2小分子抑制剂。

实验部分

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本论文所涉及中间体及终产物的¹H NMR和 ¹³C NMR核磁共振图谱由Bruker AV-300 (300 MHz) 核磁共振仪测定, 测定溶剂为氘代二甲基亚砜(DMSO-d₆) 或者氘代氯仿(CDCl₃), 内标为四甲基硅烷(TMS), 熔点由METTLER TOLEDO的MP50 Melting Point System熔点仪进行测定; 质谱由Advion小型台式质谱仪Expression CMS (EI-MS)、Agilent公司的1946A-MSD型质谱仪(ESI-MS)、Water Q-Tof型质谱仪(HRMS) 测定; 纯度由岛津高效液相(HPLC) 测定, 所用色谱柱为Agilent C18 (4.6 mm × 250 mm, 5 μm) 型反相柱; 柱层析所用的硅胶目数为200~300目(青岛海洋化学工厂), 洗脱剂所用溶剂为石油醚、二氯甲烷、乙酸乙酯、甲醇; 薄层层析色谱(TLC) 采用0.25 mm GF254薄层色谱硅胶板进行检测, 展开剂所用溶剂为石油醚、二氯甲烷、乙酸乙酯、甲醇, 通过ZF7型三用紫外分析仪观察; FP实验所用仪器为SpectaMax Multi-Mode Microplate Reader (Molecular Devices), 使用的激发光波长及发射光波长为485和535 nm。

FP实验所使用的蛋白为实验室表达并纯化的IGF2BP2蛋白, 使用的探针为5′-ATTGTCA (m⁶A) CAGCAGA-FAM-3′, 实验所用的缓冲体系为硼酸-硼砂体系(0.1 mmol·L^-1四硼酸钠, 1.6 mmol·L^-1硼酸, pH = 7.4), 实验所用的384孔黑板为Corning生产。化学实验中涉及的所有试剂原料均为化学纯或分析纯, 未注明具体来源的试剂和溶剂为市场购买的常规试剂(毕得医药、乐研试剂、上海泰坦、安耐吉化学等公司), 储存条件按照原料或商品制造厂商所建议的条件。

1 化学合成

1.1 中间体1b~28b的合成

取原料1a~28a (6.62 mmol), N-乙酰甘氨酸(3.87 g, 33.09 mmol), 乙酸钠(2.71 g, 33.09 mmol) 加入圆底烧瓶中, 加入乙酸酐20 mL, 升温至130 ℃, 加热反应4 h。TLC监测, 原料1a~28a反应完全后, 将反应液倒入20 mL冰水中, 继续搅拌15 min, 有大量黑色油状物生成。用乙酸乙酯和水萃取, 有机相用无水硫酸钠干燥, 减压蒸馏除去溶剂, 柱层析纯化得到中间体1b~28b (产率84.42%~87.21%)。

1.2 中间体1c~28c的合成

取化合物1b~28b (4.31 mmol) 于圆底烧瓶中, 加入34%盐酸水溶液, 升温至100 ℃反应2 h, 溶液由浑浊变澄清透明, 趁热过滤掉残渣, 滤液放置室温冷却过夜, 第二天有白色晶体析出, 过滤, 滤饼在烘灯下烘干, 得到中间体1c~28c白色固体(产率52.37%~60.61%)。

1.3 中间体1e~23e的合成

取原料1d~23d (5.29 mmol) 于圆底烧瓶中, 加入20 mL冰醋酸, 冰浴下搅拌10 min, 缓慢加入液溴(271 μL, ρ = 3.12 g·cm^-3, 5.29 mmol), 待体系稳定后移至室温继续反应4 h。TLC监测原料1d~23d反应完全, 向反应液加入适量冰水, 继续搅拌15 min, 体系澄清, 用乙酸乙酯和水萃取, 有机相用无水硫酸钠干燥, 减压蒸馏除去溶剂, 柱层析纯化得到中间体1e~23e (产率90.98%~98.07%)。

1.4 中间体1f~23f的合成

取原料1e~23e (3.73 mmol), 硫代氨基脲(340 mg, 3.73 mmol) 于圆底烧瓶中, 加入1, 4-二氧六环溶液20 mL室温搅拌8 h, 有大量白色沉淀析出, TLC监测原料1e~23e反应完全, 过滤, 滤饼干燥后倒入圆底烧瓶中, 加入25 mL饱和碳酸钠水溶液搅拌15 min, 白色沉淀慢慢溶解, 继续搅拌有黄色沉淀析出, 过滤, 干燥滤饼, 得到中间体1f~23f (产率84.03~90.95%)。

1.5 中间体24f的合成

取化合物13f (72 mg, 0.30 mmol), 二水氯化亚锡(343 mg, 1.52 mmol) 于圆底烧瓶中, 加入10 mL乙酸乙酯, 80 ℃加热搅拌6 h, TLC监测原料反应完全, 将反应液冷却至室温, 加入20 mL水, 冰浴下加入5 mol·L^-1 NaOH水溶液调pH至10, 体系中有白色黏稠油状物析出, 保持冰浴搅拌10 min, 抽滤, 滤饼用乙酸乙酯洗2~3次, 收集滤液用乙酸乙酯和水萃取, 有机相用无水硫酸钠干燥后减压蒸馏, 得到棕色油状物。制砂, 经柱层析纯化得到中间体24f (19 mg, 产率30.22%)。

1.6 1g~28g的合成

取中间体1c~28c (1.43 mmol), 中间体1f (373 mg, 1.43 mmol) 于50 mL圆底烧瓶中, 加入5% AcOH/EtOH 15 mL, 升温至90 ℃反应2 h。冷却至室温, 有黄色沉淀析出, 过滤, 滤饼干燥后用乙醇重结晶, 得到化合物1g~28g的E/Z式异构体(产率52.36%~58.86%)。

1.7 29g~52g的合成

以中间体10c (300.00 mg, 1.29 mmol) 和中间体2f~24f或购买的25f (1.29 mmol) 为反应原料, 按照1.6所述方法合成, 得到目标产物29g~52g的E/Z式异构体(产率65.37%~70.82%)。

化合物理化常数和波谱数据见表 1。

2 生物活性评价——IGF2BP2蛋白的FP评价方法

实验所用测试体系为60 μL, 其中蛋白、化合物、探针各20 μL, 化合物以3倍梯度稀释10~14个浓度, 每个浓度设置1个复孔。空白对照为20 μL探针+ 40 μL缓冲溶液, 阴性对照为20 μL蛋白+ 20 μL探针+ 20 μL缓冲溶液, 加完板后用锡箔纸将384孔板包住, 在摇床上室温振荡30 min, 使用仪器测定荧光偏振值, 并根据公式(1) 计算抑制率。使用GraphPad Prism计算化合物的IC₅₀值。

(1)

$抑制率(\%)=\left[1-\left(P_{\text {obs }}-P_{\min }\right) /\left(P_{\max }-P_{\min }\right)\right] \times 100$

其中, P_max、P_min、P_obs分别为IGF2BP2和荧光探针孔的偏振值、荧光探针孔的偏振值及含有抑制剂孔的偏振值。

3 分子对接方法

应用从Protein Data Bank中下载IGF2BP2 (KH3和KH4结构域) 的蛋白质晶体结构(PDB: 6ROL), 并借助Discovery Studio软件的Prepare Protein模块对蛋白结构进行初步处理, 接着通过Receptor-Ligand Interactions/Define and Edit Binding Site/From Receptor Cavities模块寻找可能的结合位点, 结合软件打分选取打分最高的潜在小分子结合位点, 并调节SBD_Site_Sphere的半径至10 Å。随后通过Prepare Ligand模块对小分子进行处理, 通过LibDock方法对小分子配体和蛋白进行分子对接, 然后对打分结果进行分析, 得到可能的小分子配体和蛋白的结合模式。

作者贡献: 张诗迪负责化合物的合成、数据的整理及文章撰写; 马赛负责化合物合成、分子对接和FP靶标活性测试工作; 王颖哲、蔡媛倩和张艳负责化合物的筛选、FP测试和可视化分析; 尤启冬负责课题规划、实验指导; 郭小可负责实验指导、文章修改及校对。

利益冲突: 本文所有作者声明不存在利益冲突关系。

基金

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国家自然科学基金资助项目(82173673)
国家自然科学基金资助项目(82473789)

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2024年第59卷第11期

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doi: 10.16438/j.0513-4870.2024-0564

接收时间：2024-06-17
首发时间：2025-11-24
出版时间：2024-11-12

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收稿日期：2024-06-17
修回日期：2024-08-18

基金

国家自然科学基金资助项目(82173673)

国家自然科学基金资助项目(82473789)

作者信息

1.中国药科大学, 江苏省药物分子设计与成药性优化重点实验室, 江苏南京 210009

2.中国药科大学药学院, 江苏南京 210009

通讯作者:

^*尤启冬, E-mail: youqd@cpu.edu.cn;

郭小可, Tel: 13701475843, E-mail: kexin95@126.com

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Cpd.	m.p., ¹H NMR, ¹³C NMR, HRMS (ESI), HPLC
1g	m.p. 207.2-208.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.12 (s, 1H), 8.06 (d, J = 2.2 Hz, 2H), 7.85-7.78 (m, 1H), 7.73-7.62 (m, 3H), 7.55 (d, J = 6.5 Hz, 2H), 4.33 (s, 1H), 4.20 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂C_l2N₄O₄S [M-H]^- 448.988 3, found 448.987 1. Purity: 95.232% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.291 min)
2g	m.p. 208.4-209.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.15 (s, 1H), 8.12 (t, J = 2.1 Hz, 1H), 7.87 (dt, J = 8.5, 2.1 Hz, 1H), 7.69 (q, J = 4.8 Hz, 2H), 7.39-7.19 (m, 5H), 4.08 (s, 1H), 3.78 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₂S [M-H]^- 404.003 2, found 404.002 2. Purity: 96.196% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.716 min)
3g	m.p. 211.2-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.15 (s, 1H), 8.10 (dd, J = 5.7, 2.0 Hz, 1H), 7.85 (dt, J = 8.4, 2.1 Hz, 1H), 7.77-7.55 (m, 2H), 7.45-6.98 (m, 4H), 4.06 (s, 1H), 3.83 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 8, found 421.992 9. Purity: 96.067% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.168 min)
4g	m.p. 211.4-212.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.17 (s, 1H), 8.08 (d, J = 2.1 Hz, 1H), 7.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.50 (dd, J = 5.8, 3.5 Hz, 1H), 7.28 (dd, J = 5.9, 3.5 Hz, 2H), 6.91 (dd, J = 5.8, 3.6 Hz, 1H), 4.08 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₃N₃O₂S [M+H]⁺ 439.978 9, found 439.977 5. Purity: 95.934% by HPLC (ACN/0.1% TFA = 50%, t_R = 7.936 min)
5g	m.p. 202.2-203.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.78 (s, 1H), 8.07 (d, J = 2.1 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.70-7.58 (m, 3H), 7.35 (dd, J = 6.6, 1.6 Hz, 2H), 7.22 (ddd, J = 7.9, 6.3, 2.8 Hz, 1H), 3.92 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂BrCl₂N₃O₂S [M+H]⁺ 483.928 3, found 485.925 7. Purity: 96.165% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.566 min)
6g	m.p. 205.1-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 11.98 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.26-7.19 (m, 1H), 7.12 (tt, J = 8.0, 6.4 Hz, 2H), 6.78-6.70 (m, 1H), 3.94 (s, 2H), 2.32 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M+H]⁺ 420.033 5, found 420.033 4. Purity: 96.421% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.537 min)
7g	m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.23 (s, 1H), 8.10 (dd, J = 5.1, 2.0 Hz, 1H), 7.85 (dd, J = 8.4, 2.1 Hz, 1H), 7.68 (dd, J = 5.4, 3.5 Hz, 2H), 7.43-7.29 (m, 1H), 7.11-7.01 (m, 3H), 4.08 (s, 1H), 3.79 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 3. Purity: 95.916% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.146 min)
8g	m.p. 203.4-204.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.11 (s, 1H), 8.11 (t, J = 2.3 Hz, 1H), 7.86 (dt, J = 8.5, 2.0 Hz, 1H), 7.73-7.62 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.03 (d, J = 7.7 Hz, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 9. Purity: 96.235% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.579 min)
9g	m.p. 213.2-214.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.22 (s, 1H), 8.11 (dd, J = 4.3, 2.0 Hz, 1H), 7.90-7.76 (m, 3H), 7.68 (d, J = 8.5 Hz, 2H), 7.53-7.40 (m, 2H), 4.12 (s, 1H), 3.83 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 169.30, 167.75, 165.99, 164.93, 140.05, 137.23, 135.40, 133.99, 133.45, 132.02, 131.45, 130.41, 129.59, 129.34, 127.94, 127.76, 126.09, 108.62, 31.36. HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 97.124% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.825 min)
10g	m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.87 (s, 1H), 12.25 (s, 1H), 8.10 (dd, J = 7.3, 2.1 Hz, 1H), 7.85 (dt, J = 8.7, 2.3 Hz, 1H), 7.60 (ddt, J = 24.7, 16.6, 8.6 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.989 5. Purity: 96.267% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.312 min)
11g	m.p. 205.2-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.41 (s, 1H), 8.21-8.07 (m, 3H), 7.86 (ddd, J = 8.6, 3.9, 2.0 Hz, 1H), 7.77-7.60 (m, 4H), 4.21 (s, 1H), 3.95 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 3, found 448.986 9. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.876 min)
12g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.27 (s, 1H), 8.11 (dd, J = 5.4, 2.0 Hz, 1H), 7.89-7.79 (m, 3H), 7.74-7.53 (m, 4H), 4.18 (s, 1H), 3.92 (s, 1H), 3.22 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₄S₂ [M+Na]⁺ 505.977 3, found 505.978 5. Purity: 96.952% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.268 min)
13g	m.p. 206.3-207.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.17 (s, 1H), 12.15 (s, 1H), 8.12 (dd, J = 5.2, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.33-7.22 (m, 2H), 7.22-7.10 (m, 2H), 4.05 (s, 1H), 3.77 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 5. Purity: 95.194% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.346 min)
14g	m.p. 205.1-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.09 (s, 1H), 8.10 (t, J = 1.9 Hz, 1H), 7.85 (dt, J = 8.5, 2.3 Hz, 1H), 7.67 (q, J = 4.6 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1H), 7.07-6.95 (m, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (d, J = 2.7 Hz, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 7. Purity: 95.268% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.826 min)
15g	m.p. 204.2-205.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.85 (s, 1H), 12.18 (s, 1H), 8.10 (dd, J = 5.3, 2.0 Hz, 1H), 7.94-7.77 (m, 3H), 7.72-7.59 (m, 2H), 7.34 (dd, J = 14.7, 8.0 Hz, 2H), 4.13 (s, 1H), 3.82 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 95.051% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.118 min)
16g	m.p. 207.4-208.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.07 (s, 1H), 8.11 (dd, J = 3.6, 2.0 Hz, 1H), 7.86 (dt, J = 8.4, 1.5 Hz, 1H), 7.73-7.62 (m, 2H), 7.15 (dd, J = 8.7, 1.8 Hz, 2H), 6.87 (dd, J = 8.7, 1.3 Hz, 2H), 3.98 (s, 1H), 3.70 (t, J = 4.7 Hz, 4H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₃S [M-H]^- 434.013 8, found 434.012 3. Purity: 96.271% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.261 min)
17g	m.p. 206.0-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.74 (s, 1H), 12.06 (s, 1H), 9.29 (d, J = 11.5 Hz, 1H), 8.12 (dd, J = 4.6, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.04 (dd, J = 8.6, 2.9 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 3.94 (s, 1H), 3.64 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₃S [M-H]^- 419.998 2, found 419.997 2. Purity: 97.629% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.561 min)
18g	m.p. 206.5-207.9 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.97 (s, 1H), 8.11 (t, J = 2.2 Hz, 1H), 7.86 (dt, J = 8.4, 1.9 Hz, 1H), 7.68 (dd, J = 7.6, 4.4 Hz, 2H), 6.99 (dd, J = 10.2, 8.0 Hz, 2H), 6.68 (dd, J = 13.7, 8.0 Hz, 2H), 3.90 (s, 1H), 3.63 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₄Cl₂N₄O₂S [M-H]^- 419.014 2, found 419.013 4. Purity: 95.081% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.146 min)
19g	m.p. 204.3-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.30 (s, 1H), 8.22 (dq, J = 8.8, 2.4 Hz, 2H), 8.11 (dd, J = 7.1, 2.0 Hz, 1H), 7.86 (dd, J = 8.4, 2.0 Hz, 1H), 7.74-7.60 (m, 2H), 7.52 (dd, J = 16.1, 8.7 Hz, 2H), 4.22 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 4, found 448.986 6. Purity: 95.967% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.591 min)
20g	m.p. 207.9-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.12 (s, 1H), 12.26 (s, 1H), 8.12 (t, J = 2.4 Hz, 1H), 7.87 (dt, J = 8.5, 1.8 Hz, 1H), 7.70 (dt, J = 8.3, 4.8 Hz, 4H), 7.47 (dd, J = 14.6, 7.9 Hz, 2H), 4.17 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.988 7. Purity: 95.181% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.173 min)
21g	m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 8.60- 8.45 (m, 2H), 8.11 (dd, J = 8.1, 2.0 Hz, 1H), 7.90-7.78 (m, 2H), 7.73-7.62 (m, 2H), 7.45 (ddd, J = 24.7, 8.0, 5.0 Hz, 1H), 4.10 (s, 1H), 3.86 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.998 2. Purity: 95.845% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.491 min)
22g	m.p. 208.3-209.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.997 1. Purity: 95.324% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.249 min)
23g	m.p. 204.1-205.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.11 (s, 1H), 8.00 (dd, J = 5.6, 2.0 Hz, 1H), 7.75 (dt, J = 8.4, 2.3 Hz, 1H), 7.64-7.53 (m, 2H), 7.32-7.16 (m, 1H), 7.14-6.65 (m, 2H), 4.00 (s, 1H), 3.80 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₁Cl₂F₂N₃O₂S [M+H]⁺ 441.999 0, found 441.999 2. Purity: 95.948% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.149 min)
24g	m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.996 4, found 491.9960. Purity: 95.945% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.159 min)
25g	m.p. 209.2-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 8.10 (dd, J = 7.4, 2.1 Hz, 1H), 7.88-7.62 (m, 4H), 7.60-7.50 (m, 1H), 7.25 (dt, J = 9.0, 7.6 Hz, 1H), 4.08 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 9, found 467.998 0. Purity: 95.461% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.591 min)
26g	m.p. 210.4-211.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.54 (s, 1H), 12.29 (s, 1H), 8.16-8.02 (m, 1H), 7.83 (td, J = 8.0, 7.3, 2.0 Hz, 1H), 7.78-7.59 (m, 3H), 7.58-7.37 (m, 2H), 4.12 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.995 8, found 491.996 4. Purity: 95.895% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.923 min)
27g	m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.04 (s, 1H), 12.86 (s, 1H), 8.08 (s, 1H), 7.96-7.79 (m, 3H), 7.70-7.62 (m, 2H), 7.32 (t, J = 9.1 Hz, 1H), 4.08 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 2, found 468.000 1. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.150 min)
28g	m.p. 209.3-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.32 (s, 1H), 8.08 (dd, J = 13.7, 2.0 Hz, 1H), 8.00 (d, J = 5.3 Hz, 2H), 7.94 (s, 1H), 7.83 (td, J = 8.7, 2.0 Hz, 1H), 7.73-7.59 (m, 2H), 4.23 (s, 1H), 4.04 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₁Cl₂F₆N₃O₂S [M+H]⁺ 541.993 2, found 541.992 6. Purity: 95.591% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.257 min)
29g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.28 (s, 1H), 12.21 (s, 1H), 7.85 (dd, J = 7.7, 3.4 Hz, 2H), 7.65-7.49 (m, 4H), 7.47-7.28 (m, 4H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₂S [M+H]⁺ 406.083 8, found 406.082 8. Purity: 96.219% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.824 min)
30g	m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.26 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.65-7.49 (m, 4H), 7.43-7.19 (m, 4H), 4.16 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.075 0. Purity: 95.193% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.781 min)
31g	m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.24 (s, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.64-7.48 (m, 5H), 7.46-7.31 (m, 3H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.044 0. Purity: 95.691% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.245 min)
32g	m.p. 203.3-204.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.14 (s, 1H), 8.58 (d, J = 4.8 Hz, 1H), 7.89 (dt, J = 14.8, 7.9 Hz, 2H), 7.69-7.48 (m, 5H), 7.34 (t, J = 5.9 Hz, 1H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.078 1. Purity: 95.015% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.228 min)
33g	m.p. 204.1-205.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 12.38 (s, 1H), 10.84 (s, 1H), 7.84 (td, J = 7.8, 1.7 Hz, 1H), 7.67-7.46 (m, 5H), 7.21-7.10 (m, 1H), 6.95-6.80 (m, 2H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 5. Purity: 95.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.629 min)
34g	m.p. 202.1-203.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.33 (s, 1H), 7.89 (s, 2H), 7.52 (d, J = 46.5 Hz, 5H), 7.24 (s, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 5. Purity: 96.018% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.104 min)
35g	m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.23 (s, 1H), 12.30 (s, 1H), 7.92-7.82 (m, 2H), 7.65-7.39 (m, 7H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 8. Purity: 95.771% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.263 min)
36g	m.p. 206.4-207.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.91 (s, 1H), 9.24 (d, J = 4.9 Hz, 1H), 8.51 (s, 3H), 8.21 (dd, J = 12.8, 4.0 Hz, 5H), 4.77 (s, 1H), 4.50 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.079 2. Purity: 95.142% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.813 min)
37g	m.p. 207.2-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.54 (s, 1H), 9.59 (s, 1H), 7.70-7.46 (m, 7H), 7.15 (s, 1H), 6.83-6.74 (m, 2H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.081 6. Purity: 95.177% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.183 min)
38g	m.p. 205.1-206.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.31 (s, 2H), 9.76 (s, 1H), 8.24-7.83 (m, 8H), 7.72-7.48 (m, 1H), 4.32 (s, 2H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.072 5. Purity: 95.834% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.102 min)
39g	m.p. 209.2-210.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.38 (s, 1H), 9.74 (s, 1H), 8.23 (s, 1H), 8.01-7.95 (m, 1H), 7.92-7.84 (m, 2H), 7.59 (d, J = 4.8 Hz, 2H), 7.16-7.07 (m, 2H), 6.51 (s, 1H), 4.26 (s, 2H), 3.85 (s, 3H). HRMS (ESI): calcd. for C₂₀H₁₆F₃N₃O₃S [M+H]⁺ 436.094 3, found 436.0933 7. Purity: 97.361% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.445 min)
40g	m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.32 (s, 1H), 8.28 (t, J = 8.8 Hz, 2H), 8.12 (d, J = 8.5 Hz, 2H), 7.85 (d, J = 4.9 Hz, 1H), 7.57 (ddd, J = 20.1, 11.3, 4.7 Hz, 4H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₃N₄O₄S [M+H]⁺ 451.068 9, found 451.068 1. Purity: 95.184% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.739 min)
41g	m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.25 (s, 1H), 8.08-8.00 (m, 2H), 7.87 (dd, J = 8.3, 5.2 Hz, 2H), 7.76 (d, J = 6.4 Hz, 1H), 7.65-7.46 (m, 4H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₃F₃N₄O₂S [M+H]⁺ 431.079 0, found 431.078 7. Purity: 96.226% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.816 min)
42g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 12.29 (s, 1H), 7.76-7.65 (m, 1H), 7.66-7.54 (m, 5H), 7.53-7.38 (m, 2H), 7.16 (dt, J = 9.9, 5.0 Hz, 1H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 8. Purity: 95.988% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.502 min)
43g	m.p. 207.2-208.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.08 (s, 1H), 12.32 (s, 1H), 7.95-7.84 (m, 2H), 7.64-7.47 (m, 4H), 7.43 (d, J = 3.4 Hz, 1H), 7.31-7.17 (m, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 9. Purity: 96.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.436 min)
44g	m.p. 211.2-212.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 9.08 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.1 Hz, 1H), 7.68-7.46 (m, 6H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.077 6. Purity: 95.901% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.195 min)
45g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.24 (s, 1H), 9.51 (s, 1H), 7.65-7.46 (m, 4H), 7.36 (s, 1H), 7.30-7.13 (m, 3H), 6.72 (d, J = 7.9 Hz, 1H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 9. Purity: 95.292% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.026 min)
46g	m.p. 205.2-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.43 (s, 1H), 13.09 (s, 1H), 12.29 (s, 1H), 8.55-8.37 (m, 1H), 8.27-8.07 (m, 1H), 8.00-7.84 (m, 1H), 7.56 (dtd, J = 12.4, 9.0, 7.8, 3.9 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.073 2. Purity: 95.723% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.273 min)
47g	m.p. 204.4-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.21 (s, 1H), 10.04 (d, J = 3.7 Hz, 1H), 7.66-7.43 (m, 6H), 7.29 (d, J = 4.9 Hz, 1H), 6.96 (td, J = 8.8, 4.0 Hz, 1H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 1. Purity: 95.519% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.523 min)
48g	m.p. 203.1-204.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.93 (s, 1H), 12.22 (s, 1H), 10.37 (s, 1H), 7.82 (dd, J = 8.2, 2.2 Hz, 1H), 7.68-7.46 (m, 5H), 7.32 (s, 1H), 6.99 (dd, J = 8.5, 2.9 Hz, 1H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.786% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.076 min)
49g	m.p. 207.3-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.25 (s, 1H), 10.11 (s, 1H), 7.79 (td, J = 9.1, 4.3 Hz, 1H), 7.64-7.43 (m, 4H), 7.10 (dd, J = 4.8, 2.4 Hz, 1H), 6.66 (dtt, J = 11.4, 4.1, 2.4 Hz, 2H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 2. Purity: 95.912% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.519 min)
50g	m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.75 (s, 1H), 12.23 (s, 1H), 10.09 (s, 1H), 7.69-7.46 (m, 5H), 7.23 (s, 1H), 6.89 (t, J = 2.4 Hz, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 4.13 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.529% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.157 min)
51g	m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.42 (s, 1H), 11.98 (s, 1H), 7.55 (ddd, J = 20.7, 7.9, 4.3 Hz, 6H), 6.98 (s, 1H), 6.59 (d, J = 8.3 Hz, 2H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₅F₃N₄O₂S [M+H]⁺ 421.094 7, found 421.093 9. Purity: 95.017% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.081 min)
52g	m.p. 205.4-206.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.61 (s, 1H), 7.76 (dd, J = 20.5, 7.8 Hz, 1H), 7.65-7.49 (m, 4H), 7.48-7.26 (m, 2H), 7.24-7.08 (m, 1H), 4.14 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂F₃N₃O₂S [M+H]⁺ 380.068 1, found 380.067 3. Purity: 95.196% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.537 min)

Cpd.

m.p., ¹H NMR, ¹³C NMR, HRMS (ESI), HPLC

m.p. 207.2-208.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.12 (s, 1H), 8.06 (d, J = 2.2 Hz, 2H), 7.85-7.78 (m, 1H), 7.73-7.62 (m, 3H), 7.55 (d, J = 6.5 Hz, 2H), 4.33 (s, 1H), 4.20 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂C_l2N₄O₄S [M-H]^- 448.988 3, found 448.987 1. Purity: 95.232% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.291 min)

m.p. 208.4-209.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.15 (s, 1H), 8.12 (t, J = 2.1 Hz, 1H), 7.87 (dt, J = 8.5, 2.1 Hz, 1H), 7.69 (q, J = 4.8 Hz, 2H), 7.39-7.19 (m, 5H), 4.08 (s, 1H), 3.78 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₂S [M-H]^- 404.003 2, found 404.002 2. Purity: 96.196% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.716 min)

m.p. 211.2-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.15 (s, 1H), 8.10 (dd, J = 5.7, 2.0 Hz, 1H), 7.85 (dt, J = 8.4, 2.1 Hz, 1H), 7.77-7.55 (m, 2H), 7.45-6.98 (m, 4H), 4.06 (s, 1H), 3.83 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 8, found 421.992 9. Purity: 96.067% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.168 min)

m.p. 211.4-212.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.17 (s, 1H), 8.08 (d, J = 2.1 Hz, 1H), 7.83 (dd, J = 8.5, 2.0 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.50 (dd, J = 5.8, 3.5 Hz, 1H), 7.28 (dd, J = 5.9, 3.5 Hz, 2H), 6.91 (dd, J = 5.8, 3.6 Hz, 1H), 4.08 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₃N₃O₂S [M+H]⁺ 439.978 9, found 439.977 5. Purity: 95.934% by HPLC (ACN/0.1% TFA = 50%, t_R = 7.936 min)

m.p. 202.2-203.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.78 (s, 1H), 8.07 (d, J = 2.1 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.70-7.58 (m, 3H), 7.35 (dd, J = 6.6, 1.6 Hz, 2H), 7.22 (ddd, J = 7.9, 6.3, 2.8 Hz, 1H), 3.92 (s, 2H). HRMS (ESI): calcd. for C₁₈H₁₂BrCl₂N₃O₂S [M+H]⁺ 483.928 3, found 485.925 7. Purity: 96.165% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.566 min)

m.p. 205.1-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 11.98 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 8.4, 2.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.26-7.19 (m, 1H), 7.12 (tt, J = 8.0, 6.4 Hz, 2H), 6.78-6.70 (m, 1H), 3.94 (s, 2H), 2.32 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M+H]⁺ 420.033 5, found 420.033 4. Purity: 96.421% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.537 min)

m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.23 (s, 1H), 8.10 (dd, J = 5.1, 2.0 Hz, 1H), 7.85 (dd, J = 8.4, 2.1 Hz, 1H), 7.68 (dd, J = 5.4, 3.5 Hz, 2H), 7.43-7.29 (m, 1H), 7.11-7.01 (m, 3H), 4.08 (s, 1H), 3.79 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 3. Purity: 95.916% by HPLC (ACN/0.1% TFA = 50%, t_R = 8.146 min)

m.p. 203.4-204.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.73 (s, 1H), 12.11 (s, 1H), 8.11 (t, J = 2.3 Hz, 1H), 7.86 (dt, J = 8.5, 2.0 Hz, 1H), 7.73-7.62 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.03 (d, J = 7.7 Hz, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 9. Purity: 96.235% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.579 min)

m.p. 213.2-214.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.22 (s, 1H), 8.11 (dd, J = 4.3, 2.0 Hz, 1H), 7.90-7.76 (m, 3H), 7.68 (d, J = 8.5 Hz, 2H), 7.53-7.40 (m, 2H), 4.12 (s, 1H), 3.83 (s, 1H). ¹³C NMR (75 MHz, DMSO-d₆) δ_C: 169.30, 167.75, 165.99, 164.93, 140.05, 137.23, 135.40, 133.99, 133.45, 132.02, 131.45, 130.41, 129.59, 129.34, 127.94, 127.76, 126.09, 108.62, 31.36. HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 97.124% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.825 min)

10g

m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.87 (s, 1H), 12.25 (s, 1H), 8.10 (dd, J = 7.3, 2.1 Hz, 1H), 7.85 (dt, J = 8.7, 2.3 Hz, 1H), 7.60 (ddt, J = 24.7, 16.6, 8.6 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.989 5. Purity: 96.267% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.312 min)

11g

m.p. 205.2-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.25 (s, 1H), 12.41 (s, 1H), 8.21-8.07 (m, 3H), 7.86 (ddd, J = 8.6, 3.9, 2.0 Hz, 1H), 7.77-7.60 (m, 4H), 4.21 (s, 1H), 3.95 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 3, found 448.986 9. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.876 min)

12g

m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.21 (s, 1H), 12.27 (s, 1H), 8.11 (dd, J = 5.4, 2.0 Hz, 1H), 7.89-7.79 (m, 3H), 7.74-7.53 (m, 4H), 4.18 (s, 1H), 3.92 (s, 1H), 3.22 (s, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₄S₂ [M+Na]⁺ 505.977 3, found 505.978 5. Purity: 96.952% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.268 min)

13g

m.p. 206.3-207.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.17 (s, 1H), 12.15 (s, 1H), 8.12 (dd, J = 5.2, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.33-7.22 (m, 2H), 7.22-7.10 (m, 2H), 4.05 (s, 1H), 3.77 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂FN₃O₂S [M-H]^- 421.993 9, found 421.992 5. Purity: 95.194% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.346 min)

14g

m.p. 205.1-206.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.09 (s, 1H), 8.10 (t, J = 1.9 Hz, 1H), 7.85 (dt, J = 8.5, 2.3 Hz, 1H), 7.67 (q, J = 4.6 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1H), 7.07-6.95 (m, 3H), 4.02 (s, 1H), 3.72 (s, 1H), 2.27 (d, J = 2.7 Hz, 3H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₂S [M-H]^- 418.018 9, found 418.017 7. Purity: 95.268% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.826 min)

15g

m.p. 204.2-205.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.85 (s, 1H), 12.18 (s, 1H), 8.10 (dd, J = 5.3, 2.0 Hz, 1H), 7.94-7.77 (m, 3H), 7.72-7.59 (m, 2H), 7.34 (dd, J = 14.7, 8.0 Hz, 2H), 4.13 (s, 1H), 3.82 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃Cl₂N₃O₄S [M-H]^- 447.993 1, found 447.992 5. Purity: 95.051% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.118 min)

16g

m.p. 207.4-208.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.13 (s, 1H), 12.07 (s, 1H), 8.11 (dd, J = 3.6, 2.0 Hz, 1H), 7.86 (dt, J = 8.4, 1.5 Hz, 1H), 7.73-7.62 (m, 2H), 7.15 (dd, J = 8.7, 1.8 Hz, 2H), 6.87 (dd, J = 8.7, 1.3 Hz, 2H), 3.98 (s, 1H), 3.70 (t, J = 4.7 Hz, 4H). HRMS (ESI): calcd. for C₁₉H₁₅Cl₂N₃O₃S [M-H]^- 434.013 8, found 434.012 3. Purity: 96.271% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.261 min)

17g

m.p. 206.0-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.74 (s, 1H), 12.06 (s, 1H), 9.29 (d, J = 11.5 Hz, 1H), 8.12 (dd, J = 4.6, 2.0 Hz, 1H), 7.87 (dd, J = 8.4, 2.1 Hz, 1H), 7.74-7.63 (m, 2H), 7.04 (dd, J = 8.6, 2.9 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 3.94 (s, 1H), 3.64 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃Cl₂N₃O₃S [M-H]^- 419.998 2, found 419.997 2. Purity: 97.629% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.561 min)

18g

m.p. 206.5-207.9 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.97 (s, 1H), 8.11 (t, J = 2.2 Hz, 1H), 7.86 (dt, J = 8.4, 1.9 Hz, 1H), 7.68 (dd, J = 7.6, 4.4 Hz, 2H), 6.99 (dd, J = 10.2, 8.0 Hz, 2H), 6.68 (dd, J = 13.7, 8.0 Hz, 2H), 3.90 (s, 1H), 3.63 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₄Cl₂N₄O₂S [M-H]^- 419.014 2, found 419.013 4. Purity: 95.081% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.146 min)

19g

m.p. 204.3-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.30 (s, 1H), 8.22 (dq, J = 8.8, 2.4 Hz, 2H), 8.11 (dd, J = 7.1, 2.0 Hz, 1H), 7.86 (dd, J = 8.4, 2.0 Hz, 1H), 7.74-7.60 (m, 2H), 7.52 (dd, J = 16.1, 8.7 Hz, 2H), 4.22 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₂Cl₂N₄O₄S [M-H]^- 448.988 4, found 448.986 6. Purity: 95.967% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.591 min)

20g

m.p. 207.9-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.12 (s, 1H), 12.26 (s, 1H), 8.12 (t, J = 2.4 Hz, 1H), 7.87 (dt, J = 8.5, 1.8 Hz, 1H), 7.70 (dt, J = 8.3, 4.8 Hz, 4H), 7.47 (dd, J = 14.6, 7.9 Hz, 2H), 4.17 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂F₃N₃O₂S [M-H]^- 471.990 7, found 471.988 7. Purity: 95.181% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.173 min)

21g

m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 8.60- 8.45 (m, 2H), 8.11 (dd, J = 8.1, 2.0 Hz, 1H), 7.90-7.78 (m, 2H), 7.73-7.62 (m, 2H), 7.45 (ddd, J = 24.7, 8.0, 5.0 Hz, 1H), 4.10 (s, 1H), 3.86 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.998 2. Purity: 95.845% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.491 min)

22g

m.p. 208.3-209.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂Cl₂N₄O₂S [M-H]^- 404.998 5, found 404.997 1. Purity: 95.324% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.249 min)

23g

m.p. 204.1-205.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.11 (s, 1H), 8.00 (dd, J = 5.6, 2.0 Hz, 1H), 7.75 (dt, J = 8.4, 2.3 Hz, 1H), 7.64-7.53 (m, 2H), 7.32-7.16 (m, 1H), 7.14-6.65 (m, 2H), 4.00 (s, 1H), 3.80 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₁Cl₂F₂N₃O₂S [M+H]⁺ 441.999 0, found 441.999 2. Purity: 95.948% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.149 min)

24g

m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.86 (s, 1H), 12.44 (s, 1H), 8.61 (d, J = 5.0 Hz, 2H), 8.20 (dd, J = 4.7, 2.0 Hz, 1H), 7.95 (dd, J = 8.4, 2.1 Hz, 1H), 7.83-7.70 (m, 2H), 7.41 (dd, J = 44.8, 5.0 Hz, 2H), 4.20 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.996 4, found 491.9960. Purity: 95.945% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.159 min)

25g

m.p. 209.2-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 8.10 (dd, J = 7.4, 2.1 Hz, 1H), 7.88-7.62 (m, 4H), 7.60-7.50 (m, 1H), 7.25 (dt, J = 9.0, 7.6 Hz, 1H), 4.08 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 9, found 467.998 0. Purity: 95.461% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.591 min)

26g

m.p. 210.4-211.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.54 (s, 1H), 12.29 (s, 1H), 8.16-8.02 (m, 1H), 7.83 (td, J = 8.0, 7.3, 2.0 Hz, 1H), 7.78-7.59 (m, 3H), 7.58-7.37 (m, 2H), 4.12 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₁Cl₂F₄N₃O₂S [M+H]⁺ 491.995 8, found 491.996 4. Purity: 95.895% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.923 min)

27g

m.p. 212.1-213.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.04 (s, 1H), 12.86 (s, 1H), 8.08 (s, 1H), 7.96-7.79 (m, 3H), 7.70-7.62 (m, 2H), 7.32 (t, J = 9.1 Hz, 1H), 4.08 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₂Cl₂FN₃O₄S [M+H]⁺ 467.998 2, found 468.000 1. Purity: 95.146% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.150 min)

28g

m.p. 209.3-210.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.32 (s, 1H), 8.08 (dd, J = 13.7, 2.0 Hz, 1H), 8.00 (d, J = 5.3 Hz, 2H), 7.94 (s, 1H), 7.83 (td, J = 8.7, 2.0 Hz, 1H), 7.73-7.59 (m, 2H), 4.23 (s, 1H), 4.04 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₁Cl₂F₆N₃O₂S [M+H]⁺ 541.993 2, found 541.992 6. Purity: 95.591% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.257 min)

29g

m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.28 (s, 1H), 12.21 (s, 1H), 7.85 (dd, J = 7.7, 3.4 Hz, 2H), 7.65-7.49 (m, 4H), 7.47-7.28 (m, 4H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₂S [M+H]⁺ 406.083 8, found 406.082 8. Purity: 96.219% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.824 min)

30g

m.p. 208.2-209.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.26 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.65-7.49 (m, 4H), 7.43-7.19 (m, 4H), 4.16 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.075 0. Purity: 95.193% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.781 min)

31g

m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.72 (s, 1H), 12.24 (s, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.64-7.48 (m, 5H), 7.46-7.31 (m, 3H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.044 0. Purity: 95.691% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.245 min)

32g

m.p. 203.3-204.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.14 (s, 1H), 8.58 (d, J = 4.8 Hz, 1H), 7.89 (dt, J = 14.8, 7.9 Hz, 2H), 7.69-7.48 (m, 5H), 7.34 (t, J = 5.9 Hz, 1H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.078 1. Purity: 95.015% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.228 min)

33g

m.p. 204.1-205.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 12.38 (s, 1H), 10.84 (s, 1H), 7.84 (td, J = 7.8, 1.7 Hz, 1H), 7.67-7.46 (m, 5H), 7.21-7.10 (m, 1H), 6.95-6.80 (m, 2H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 5. Purity: 95.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.629 min)

34g

m.p. 202.1-203.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.94 (s, 1H), 12.33 (s, 1H), 7.89 (s, 2H), 7.52 (d, J = 46.5 Hz, 5H), 7.24 (s, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 5. Purity: 96.018% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.104 min)

35g

m.p. 206.3-207.5 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.23 (s, 1H), 12.30 (s, 1H), 7.92-7.82 (m, 2H), 7.65-7.39 (m, 7H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 8. Purity: 95.771% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.263 min)

36g

m.p. 206.4-207.8 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.91 (s, 1H), 9.24 (d, J = 4.9 Hz, 1H), 8.51 (s, 3H), 8.21 (dd, J = 12.8, 4.0 Hz, 5H), 4.77 (s, 1H), 4.50 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.079 2. Purity: 95.142% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.813 min)

37g

m.p. 207.2-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.54 (s, 1H), 9.59 (s, 1H), 7.70-7.46 (m, 7H), 7.15 (s, 1H), 6.83-6.74 (m, 2H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.081 6. Purity: 95.177% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.183 min)

38g

m.p. 205.1-206.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.31 (s, 2H), 9.76 (s, 1H), 8.24-7.83 (m, 8H), 7.72-7.48 (m, 1H), 4.32 (s, 2H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.072 5. Purity: 95.834% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.102 min)

39g

m.p. 209.2-210.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.38 (s, 1H), 9.74 (s, 1H), 8.23 (s, 1H), 8.01-7.95 (m, 1H), 7.92-7.84 (m, 2H), 7.59 (d, J = 4.8 Hz, 2H), 7.16-7.07 (m, 2H), 6.51 (s, 1H), 4.26 (s, 2H), 3.85 (s, 3H). HRMS (ESI): calcd. for C₂₀H₁₆F₃N₃O₃S [M+H]⁺ 436.094 3, found 436.0933 7. Purity: 97.361% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.445 min)

40g

m.p. 206.1-207.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.95 (s, 1H), 12.32 (s, 1H), 8.28 (t, J = 8.8 Hz, 2H), 8.12 (d, J = 8.5 Hz, 2H), 7.85 (d, J = 4.9 Hz, 1H), 7.57 (ddd, J = 20.1, 11.3, 4.7 Hz, 4H), 4.16 (s, 1H), 3.91 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₃N₄O₄S [M+H]⁺ 451.068 9, found 451.068 1. Purity: 95.184% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.739 min)

41g

m.p. 211.1-212.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.07 (s, 1H), 12.25 (s, 1H), 8.08-8.00 (m, 2H), 7.87 (dd, J = 8.3, 5.2 Hz, 2H), 7.76 (d, J = 6.4 Hz, 1H), 7.65-7.46 (m, 4H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₃F₃N₄O₂S [M+H]⁺ 431.079 0, found 431.078 7. Purity: 96.226% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.816 min)

42g

m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.99 (s, 1H), 12.29 (s, 1H), 7.76-7.65 (m, 1H), 7.66-7.54 (m, 5H), 7.53-7.38 (m, 2H), 7.16 (dt, J = 9.9, 5.0 Hz, 1H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₂S [M+H]⁺ 424.074 4, found 424.074 8. Purity: 95.988% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.502 min)

43g

m.p. 207.2-208.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.08 (s, 1H), 12.32 (s, 1H), 7.95-7.84 (m, 2H), 7.64-7.47 (m, 4H), 7.43 (d, J = 3.4 Hz, 1H), 7.31-7.17 (m, 2H), 4.15 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₂S [M+H]⁺ 440.044 8, found 440.043 9. Purity: 96.117% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.436 min)

44g

m.p. 211.2-212.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.03 (s, 1H), 9.08 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.1 Hz, 1H), 7.68-7.46 (m, 6H), 4.16 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₈H₁₃F₃N₄O₂S [M+H]⁺ 407.079 0, found 407.077 6. Purity: 95.901% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.195 min)

45g

m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.24 (s, 1H), 9.51 (s, 1H), 7.65-7.46 (m, 4H), 7.36 (s, 1H), 7.30-7.13 (m, 3H), 6.72 (d, J = 7.9 Hz, 1H), 4.15 (s, 1H), 3.90 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₄F₃N₃O₃S [M+H]⁺ 422.078 7, found 422.078 9. Purity: 95.292% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.026 min)

46g

m.p. 205.2-206.3 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.43 (s, 1H), 13.09 (s, 1H), 12.29 (s, 1H), 8.55-8.37 (m, 1H), 8.27-8.07 (m, 1H), 8.00-7.84 (m, 1H), 7.56 (dtd, J = 12.4, 9.0, 7.8, 3.9 Hz, 6H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₂₀H₁₄F₃N₃O₄S [M+H]⁺ 450.073 6, found 450.073 2. Purity: 95.723% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.273 min)

47g

m.p. 204.4-205.6 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.92 (s, 1H), 12.21 (s, 1H), 10.04 (d, J = 3.7 Hz, 1H), 7.66-7.43 (m, 6H), 7.29 (d, J = 4.9 Hz, 1H), 6.96 (td, J = 8.8, 4.0 Hz, 1H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 1. Purity: 95.519% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.523 min)

48g

m.p. 203.1-204.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.93 (s, 1H), 12.22 (s, 1H), 10.37 (s, 1H), 7.82 (dd, J = 8.2, 2.2 Hz, 1H), 7.68-7.46 (m, 5H), 7.32 (s, 1H), 6.99 (dd, J = 8.5, 2.9 Hz, 1H), 4.14 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.786% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.076 min)

49g

m.p. 207.3-208.4 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.20 (s, 1H), 12.25 (s, 1H), 10.11 (s, 1H), 7.79 (td, J = 9.1, 4.3 Hz, 1H), 7.64-7.43 (m, 4H), 7.10 (dd, J = 4.8, 2.4 Hz, 1H), 6.66 (dtt, J = 11.4, 4.1, 2.4 Hz, 2H), 4.15 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃F₄N₃O₃S [M+H]⁺ 440.069 3, found 440.069 2. Purity: 95.912% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.519 min)

50g

m.p. 207.1-208.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.75 (s, 1H), 12.23 (s, 1H), 10.09 (s, 1H), 7.69-7.46 (m, 5H), 7.23 (s, 1H), 6.89 (t, J = 2.4 Hz, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 4.13 (s, 1H), 3.89 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₃ClF₃N₃O₃S [M+H]⁺ 456.039 7, found 456.039 0. Purity: 95.529% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.157 min)

51g

m.p. 208.0-209.2 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 13.42 (s, 1H), 11.98 (s, 1H), 7.55 (ddd, J = 20.7, 7.9, 4.3 Hz, 6H), 6.98 (s, 1H), 6.59 (d, J = 8.3 Hz, 2H), 4.14 (s, 1H), 3.88 (s, 1H). HRMS (ESI): calcd. for C₁₉H₁₅F₃N₄O₂S [M+H]⁺ 421.094 7, found 421.093 9. Purity: 95.017% by HPLC (ACN/0.1%TFA = 50%, t_R = 7.081 min)

52g

m.p. 205.4-206.7 ℃. ¹H NMR (300 MHz, DMSO-d₆) δ_H: 12.61 (s, 1H), 7.76 (dd, J = 20.5, 7.8 Hz, 1H), 7.65-7.49 (m, 4H), 7.48-7.26 (m, 2H), 7.24-7.08 (m, 1H), 4.14 (s, 1H), 3.92 (s, 1H). HRMS (ESI): calcd. for C₁₇H₁₂F₃N₃O₂S [M+H]⁺ 380.068 1, found 380.067 3. Purity: 95.196% by HPLC (ACN/0.1%TFA = 50%, t_R = 8.537 min)


1g		23.06 ± 5.08	2g	11.35 ± 1.77
3g	7.53 ± 0.37	4g	10.48 ± 1.59
5g	45.40 ± 5.23	6g	17.03 ± 0.45
7g	10.48 ± 2.92	8g	8.01 ± 0.47
9g	0.97 ± 0.08	10g	6.81 ± 0.64
11g	7.17 ± 0.38	12g	10.48 ± 1.15
13g	11.35 ± 1.26	14g	13.62 ± 0.72
15g	3.24 ± 0.59	16g	17.03 ± 1.83
17g	17.03 ± 2.26	18g	27.24 ± 3.09
19g	8.01 ± 0.73	20g	11.35 ± 1.75
21g	13.26 ± 1.07	22g	9.73 ± 0.56
23g	12.38 ± 1.06	24g	6.75 ± 0.53
25g	1.70 ± 0.11	26g	6.49 ± 0.31
27g	5.24 ± 0.45	28g	6.49 ± 0.89

Cpd.

R₁

IC₅₀/μmol·L^-1

Cpd.

R₁

IC₅₀/μmol·L^-1

23.06 ± 5.08

11.35 ± 1.77

7.53 ± 0.37

10.48 ± 1.59

45.40 ± 5.23

17.03 ± 0.45

10.48 ± 2.92

8.01 ± 0.47

0.97 ± 0.08

10g

6.81 ± 0.64

11g

7.17 ± 0.38

12g

10.48 ± 1.15

13g

11.35 ± 1.26

14g

13.62 ± 0.72

15g

3.24 ± 0.59

16g

17.03 ± 1.83

17g

17.03 ± 2.26

18g

27.24 ± 3.09

19g

8.01 ± 0.73

20g

11.35 ± 1.75

21g

13.26 ± 1.07

22g

9.73 ± 0.56

23g

12.38 ± 1.06

24g

6.75 ± 0.53

25g

1.70 ± 0.11

26g

6.49 ± 0.31

27g

5.24 ± 0.45

28g

6.49 ± 0.89


29g		9.88 ± 1.32	30g	7.12 ± 0.87
31g	5.82 ± 0.46	32g	26.35 ± 1.89
33g	15.21 ± 1.76	34g	7.08 ± 0.83
35g	10.19 ± 1.52	36g	> 100
37g	1.90 ± 0.21	38g	9.55 ± 1.23
39g	> 200	40g	6.77 ± 0.53
41g	14.55 ± 1.23	42g	7.07 ± 0.67
43g	8.77 ± 0.94	44g	28.93 ± 2.25
45g	9.61 ± 1.06	46g	4.81 ± 0.59
47g	1.33 ± 0.08	48g	4.36 ± 0.33
49g	5.81 ± 0.61	50g	9.45 ± 0.27
51g	4.48 ± 0.12	52g	1.41 ± 0.54

Cpd.

R₂

IC₅₀/μmol·L^-1

Cpd.

R₂

IC₅₀/μmol·L^-1

29g

9.88 ± 1.32

30g

7.12 ± 0.87

31g

5.82 ± 0.46

32g

26.35 ± 1.89

33g

15.21 ± 1.76

34g

7.08 ± 0.83

35g

10.19 ± 1.52

36g

> 100

37g

1.90 ± 0.21

38g

9.55 ± 1.23

39g

> 200

40g

6.77 ± 0.53

41g

14.55 ± 1.23

42g

7.07 ± 0.67

43g

8.77 ± 0.94

44g

28.93 ± 2.25

45g

9.61 ± 1.06

46g

4.81 ± 0.59

47g

1.33 ± 0.08

48g

4.36 ± 0.33

49g

5.81 ± 0.61

50g

9.45 ± 0.27

51g

4.48 ± 0.12

52g

1.41 ± 0.54