With this context, we report the design, synthesis and pharmacological profiles of some novel multi-functional anti-AD agents K1383CK1389 containing 6-Cl-THA and scutellarin fragments. g BChE from human being plasma. 2.2.2. Kinetic Analysis To determine the connection of K1383 with 0.05), consistent with graphical representation of corresponding Lineweaver-Burk storyline in Figure 2, where all the lines intersect on the one point of the C), 56.0, 31.9. 3.4. (E)-3-(4-Bromophenyl)-1-(6-hydroxy-2,3,4-trimethoxyphenyl)-prop-2-en-1-one = 15.7 Hz, 1H), 7.74 (d, = 15.7 Hz, 1H), 7.55 (d, = 8.3 Hz, 2H), 7.50 (d, = 8.3 Hz, 2H), 6.30 (s, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.84 (s, 3H); 13C-NMR (CDCl3) 198.9, 169.0, 166.7, 161.2, 147.9, 141.6, 140.6, 138.7, 138.5, 137.3, 136.0, 133.5, 130.8, 114.9, 102.9, 68.2, 67.6, 62.4. 3.5. 2-(4-Bromophenyl)-5,6,7-trimethoxy-4H-chromen-4-one (K1383). m.p.: 123.7C128.1 C. Yield: 40%. 1H-NMR (CDCl3) 7.96 (m, 2H), 7.67 (d, = 8.8 Hz, 2H), 7.23 (dd, = 9.0, 2.1 Hz, 1H), ABT-492 (Delafloxacin) 6.78 (s, 1H), 6.71 (d, = 8.8 Hz, 2H), 6.49 (s, 1H), 3.98 (s, 3H), 3.98 (s, 3H), 3.92 (s, 3H), 3.87 (t, = 5.4 Hz, 2H), 3.54 (m, 2H), 3.04 (m, 2H), 2.67 (m, 2H), 1.85 (m, 4H); 13C-NMR (CDCl3) 177.2, 161.7, 157.5, 154.4, 152.4, 151.4, 150.5, 140.2, 135.2, 128.2, 127.6 (2 C), 125.0, 124.5, 120.1, 117.7, 115.8, 112.7, 112.7 (2 C), 150.6, 96.2, 62.2, 61.5, 56.3, 47.6, 44.1, 29.7, 24.7, 22.6, 22.0, ESI-HRMS: 293.6068 [M + 2H]+ (calculated for: [C33H33ClN3O5]+/2 293.6000). (K1384). m.p.: 103.6C106.3 C. Yield: 15%. 1H-NMR (CDCl3) 8.00 (d, = 9.1 Hz, 1H), 7.94 (d, = 2.1 Hz, 1H), 7.66 (d, = 8.5 Hz, 2H), 7.17 (m, 2H), 6.77 (s, 1H), 6.73 (d, = 8.6 Hz, 2H), 6.48 (s, 1H), 3.98 (s, 3H), 3.98 (s, 3H), 3.92 (s, 3H), 3.87 (t, = 6.4 Hz, 2H), 3.43 (m, 2H), 3.02 (d, = 6.0 Hz, 2H), 2.62 (d, = 5.4 Hz, 2H), 2.12 (d, = 6.4 Hz, 2H), 1.85 (m, 4H); 13C-NMR (CDCl3) 177.2, 161.9, 157.4, 154.4, 152.4, 150.7, 140.2, 135.8, 128.9, 128.7, 128.2, 127.5 (2 C), 125.3, 125.2, 124.9, 119.5, 112.7, 112.5 (2 C), 105.4, 96.2, 62.2, 61.5, 56.3, 46.9, 41.1, 30.1, 29.7, 24.5, 22.4, 21.6, ESI-HRMS: 300.6164 [M + 2H]+ (calculated for: [C34H35ClN3O5]+/2 300.6079). (K1385). m.p.: 102.1C104.5 C. Yield: 64%. 1H-NMR (CDCl3) 7.98 (d, = 9.1 Hz, 1H), 7.91 (d, = 2.2 Hz, 1H), 7.61 (m, 2H), 7.19 (dd, = 9.1, 2.2 Hz, 1H), 6.77 (s, 1H), 6.65 (m, 2H), 6.47 (s, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.90 (s, 3H), 3.68 (t, = 7.0 Hz, 2H), 3.24 (t, = 6.6 Hz, 2H), 3.03 (m, 2H), 2.62 (m, 2H), 1.85 (m, 6H), 1.77 (m, 2H); 13C-NMR (CDCl3) 177.2, 161.9, 157.4, 156.6, 154.4, 152.4, 152.2, 150.8, 143.0, 140.1, 135.5, 131.2, 130.9, 127.5, 125.0, 124.7, 124.0, 119.0, 116.8, 114.0, 112.7, 112.2, 105.2, 96.2, 62.1, 61.5, 56.2, 42.8, 31.6, 29.6, 28.9, 26.3, 24.6, 22.5, 21.7, ESI-HRMS: 307.6243 [M + 2H]+ (calculated ABT-492 (Delafloxacin) for: [C35H37ClN3O5]/2+ 307.6157). (K1386). m.p.: 84.9C87.5 C. Yield: 88%. 1H-NMR (CDCl3) 7.97 (m, 2H), 7.64 (m, 2H), 7.22 (dd, = 9.1, 2.2 Hz, 1H), 6.76 (s, 1H), 6.62 (m, 2H), 6.47 (s, 1H), 3.97 ABT-492 (Delafloxacin) (s, 3H), 3.96 (s, 3H), 3.90 (s, 3H), 3.64 (t, = 7.1 Hz, 2H), 3.19 (t, = 6.8 Hz, 2H), 3.04 (m, 2H), 2.65 (m, 2H), 1.86 (m, 4H), 1.78 (m, 2H), 1.70 (m, 2H), 1.55 (m, 2H); 13C-NMR (CDCl3) 177.3, 161.9, 157.4, 154.4, 152.5, 152.3, 150.9, 140.1, 139.3, 135.5, 127.5 (2 C), 125.1, 124.8, 119.0, 116.9, 114.0, 112.8, 112.2 (2 C), 105.2, 96.2, 62.2, 61.5, 58.4, 56.3, 50.7, 48.8, 43.0, 31.9, 31.2, 29.7 (2 C), 28.8; ESI-HRMS: 314.6320 [M + 2H]+ (calculated for: [C36H39ClN3O5]+/2 314.6235). (K1387). m.p.: 74.9C77.3 C. Yield: 67%. 1H-NMR (CDCl3) 8.02 (m, 2H), 7.68 (m, 2H), 7.24 (dd, = 9.1, 2.1 Hz, 1H), 6.77 (s, 1H), 6.64 (m, 2H), 6.49 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H), 3.91 (s, 3H), 3.68 (t, = 7.2 Hz, 2H), 3.18 (t, = 6.9 Hz, 2H), 3.07 (m, 2H), 2.66 (m, 2H), 1.88 (m, 4H), 1.76 (m, 2H), 1.68 (m, 2H), 1.48 (m, 4H); 13C-NMR (CDCl3) 177.3, 162.0, 157.4, 154.4, 152.5, 151.0, 140.1, 139.3, 127.5 (2 C), 125.2, 124.8, 124.5, 123.9, 123.4, 119.0, 114.0, 112.8, 112.2 (2 C), 105.2, 96.2, 62.2, 61.5, 56.3, 48.7, 43.2, 33.8, 31.9, 31.6, 31.4 (2 C), 26.7, 26.5, 24.5; ESI-HRMS: 321.6399 [M + 2H]+ (calculated for: [C37H41ClN3O5]+/2 321.6314). (K1388). m.p.: 82.4C86.8 C. Yield: 60%. 1H-NMR (CDCl3) 7.98 (m, 2H), 7.67 (d, = 8.8 Hz, 2H), 7.25 (dd, = 9.0, 2.2 Hz,.All authors contributed to and have approved the final manuscript. Conflicts of Interest The authors declare no conflict of interest. Footnotes Sample Availability: Samples of the compounds K1383CK1389 are available from the authors.. spectral data were in good agreement with the literature characterization [46]. The treatment of 8 with appropriate 1,-diamines in the presence of phenol afforded the required AChE activity; e BChE from equine serum; f AChE from human being erythrocytes; g BChE from human being plasma. 2.2.2. Kinetic Analysis To determine the connection of K1383 with 0.05), consistent with graphical representation of corresponding Lineweaver-Burk storyline in Figure 2, where all the lines intersect on the one point of the C), 56.0, 31.9. 3.4. (E)-3-(4-Bromophenyl)-1-(6-hydroxy-2,3,4-trimethoxyphenyl)-prop-2-en-1-one = 15.7 Hz, 1H), 7.74 (d, = 15.7 Hz, 1H), 7.55 (d, = 8.3 Hz, 2H), 7.50 (d, = 8.3 Hz, 2H), 6.30 (s, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.84 (s, 3H); 13C-NMR (CDCl3) 198.9, 169.0, 166.7, 161.2, 147.9, 141.6, 140.6, 138.7, 138.5, 137.3, 136.0, 133.5, 130.8, 114.9, 102.9, 68.2, 67.6, 62.4. 3.5. 2-(4-Bromophenyl)-5,6,7-trimethoxy-4H-chromen-4-one (K1383). m.p.: 123.7C128.1 C. Yield: 40%. 1H-NMR (CDCl3) 7.96 (m, 2H), 7.67 (d, = 8.8 Hz, 2H), 7.23 (dd, = 9.0, 2.1 Hz, 1H), 6.78 (s, 1H), 6.71 (d, = 8.8 Hz, 2H), 6.49 (s, 1H), 3.98 (s, 3H), 3.98 (s, 3H), 3.92 (s, 3H), 3.87 (t, = 5.4 Hz, 2H), 3.54 (m, 2H), 3.04 (m, 2H), 2.67 (m, 2H), 1.85 (m, 4H); 13C-NMR (CDCl3) 177.2, 161.7, 157.5, 154.4, 152.4, 151.4, 150.5, 140.2, 135.2, 128.2, 127.6 (2 C), 125.0, 124.5, 120.1, 117.7, 115.8, 112.7, Rabbit Polyclonal to CDCA7 112.7 (2 C), 150.6, 96.2, 62.2, 61.5, 56.3, 47.6, 44.1, 29.7, 24.7, 22.6, 22.0, ESI-HRMS: 293.6068 [M + 2H]+ (calculated for: [C33H33ClN3O5]+/2 293.6000). (K1384). m.p.: 103.6C106.3 C. Yield: 15%. 1H-NMR (CDCl3) 8.00 (d, = 9.1 Hz, 1H), 7.94 (d, = 2.1 Hz, 1H), 7.66 (d, = 8.5 Hz, 2H), 7.17 (m, 2H), 6.77 (s, 1H), 6.73 (d, = 8.6 Hz, 2H), 6.48 (s, 1H), 3.98 (s, 3H), 3.98 (s, 3H), 3.92 (s, 3H), 3.87 (t, = 6.4 Hz, 2H), 3.43 (m, 2H), 3.02 (d, = 6.0 Hz, 2H), 2.62 (d, = 5.4 Hz, 2H), 2.12 (d, = 6.4 Hz, 2H), 1.85 (m, 4H); 13C-NMR (CDCl3) 177.2, 161.9, 157.4, 154.4, 152.4, 150.7, 140.2, 135.8, 128.9, 128.7, 128.2, 127.5 (2 C), 125.3, 125.2, 124.9, 119.5, 112.7, 112.5 (2 C), 105.4, 96.2, 62.2, 61.5, 56.3, 46.9, 41.1, 30.1, 29.7, 24.5, 22.4, 21.6, ESI-HRMS: 300.6164 [M + 2H]+ (calculated for: [C34H35ClN3O5]+/2 300.6079). (K1385). m.p.: 102.1C104.5 C. Yield: 64%. 1H-NMR (CDCl3) 7.98 (d, = 9.1 Hz, 1H), 7.91 (d, = 2.2 Hz, 1H), 7.61 (m, 2H), 7.19 (dd, = 9.1, 2.2 Hz, 1H), 6.77 (s, 1H), 6.65 (m, 2H), 6.47 (s, 1H), 3.98 (s, 3H), 3.96 (s, 3H), 3.90 (s, 3H), 3.68 (t, = 7.0 Hz, 2H), 3.24 (t, = 6.6 Hz, 2H), 3.03 (m, 2H), 2.62 (m, 2H), 1.85 (m, 6H), 1.77 (m, 2H); 13C-NMR (CDCl3) 177.2, 161.9, 157.4, 156.6, 154.4, 152.4, 152.2, 150.8, 143.0, 140.1, 135.5, 131.2, 130.9, 127.5, 125.0, 124.7, 124.0, 119.0, 116.8, 114.0, 112.7, 112.2, 105.2, 96.2, 62.1, 61.5, 56.2, 42.8, 31.6, 29.6, 28.9, 26.3, 24.6, 22.5, 21.7, ESI-HRMS: 307.6243 [M + 2H]+ (calculated for: [C35H37ClN3O5]/2+ 307.6157). (K1386). m.p.: 84.9C87.5 C. Yield: 88%. 1H-NMR (CDCl3) 7.97 (m, 2H), 7.64 (m, 2H), 7.22 (dd, = 9.1, 2.2 Hz, 1H), 6.76 (s, 1H), 6.62 (m, 2H), 6.47 (s, 1H), 3.97 (s, 3H), 3.96 (s, 3H), 3.90 (s, 3H), 3.64 (t, = 7.1 Hz, 2H), 3.19 (t, = 6.8 Hz, 2H), 3.04 (m, 2H), 2.65 (m, 2H), 1.86 (m, 4H), 1.78 (m, 2H), 1.70 (m, 2H), 1.55 (m, 2H); 13C-NMR (CDCl3) 177.3, 161.9, 157.4, 154.4, 152.5, 152.3, 150.9, 140.1, 139.3, 135.5, 127.5 (2 C), 125.1, 124.8, 119.0, 116.9, 114.0, 112.8, 112.2 (2 C), 105.2, 96.2, 62.2, 61.5, 58.4, 56.3, 50.7, 48.8, 43.0, 31.9, 31.2, 29.7 (2 C), 28.8; ESI-HRMS: 314.6320 [M + 2H]+ (calculated for: [C36H39ClN3O5]+/2 314.6235). (K1387). m.p.: 74.9C77.3 C. Yield: 67%. 1H-NMR (CDCl3) 8.02 (m, 2H), 7.68 (m, 2H), 7.24 (dd, = 9.1, 2.1 Hz, 1H), 6.77 (s, 1H), 6.64 (m, 2H), 6.49 (s, 1H), 3.98 (s, 3H), 3.97 (s, 3H), 3.91 (s, 3H), 3.68 (t, = 7.2 Hz, 2H), 3.18 (t, = 6.9 Hz, 2H), 3.07 (m, 2H), 2.66 (m, 2H), 1.88 (m, 4H), 1.76 (m, 2H), 1.68 (m, 2H), 1.48 (m, 4H); 13C-NMR (CDCl3) 177.3, 162.0, 157.4, 154.4, 152.5, 151.0, 140.1, 139.3, 127.5 (2 C), 125.2, 124.8, 124.5, 123.9, 123.4, 119.0, 114.0, 112.8, 112.2 (2 C), 105.2, 96.2, 62.2, 61.5, 56.3, 48.7, 43.2, 33.8, 31.9, 31.6, 31.4 (2 C), 26.7, 26.5, 24.5; ESI-HRMS: 321.6399 [M + 2H]+ (calculated for: [C37H41ClN3O5]+/2 321.6314). (K1388). m.p.: 82.4C86.8 C. Yield: 60%. 1H-NMR (CDCl3) 7.98 (m, 2H), 7.67 (d, = 8.8 Hz, 2H), 7.25 (dd, = 9.0, 2.2 Hz,.