A.A.-M. Abdel-Aziz, et al.
BioorganicChemistry87(2019)425–431
J = 7.9 Hz), 7.05 (1H, d, J = 7.4 Hz), 7.11 (1H, t, J = 7.4 Hz), 7.45
(3H, d, J = 6.9 Hz), 7.53 (2H, s), 7.71 (2H, d, J = 6.8 Hz), 7.95 (2H, d,
J = 7.6 Hz), 8.03 (2H, d, J = 7.5 Hz), 9.79 (1H, s); 13C NMR (176 MHz,
DMSO‑d6): δ 40.93, 57.26, 115.98, 119.43, 125.60, 127.22, 127.77,
128.79, 129.27, 130.38, 130.93, 131.50, 138.41, 146.04, 154.68,
156.93, 164.67; C22H19N3O4S: m/z (421.4).
129.27, 130.47, 130.54, 138.29, 142.81, 146.00, 147.37, 155.38,
160.06, 163.06; C24H23N3O5S: m/z (465.5).
4.1.1.14. 4-(3-(2,4-Dimethoxyphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-
1H-pyrazole-1-carbonyl)benzenesulfonamide (31). M.P. 271–273 °C,
88% yield (CH3OH); IR (KBr, cm−1) ν: 3328, 3218 (NH2), 1668 (C]
O), 1619 (C]N), 1335, 1161 (O]S]O); 1H NMR (700 MHz,
DMSO‑d6): δ 3.16 (1H, dd, J = 18.4 Hz, 4.4 Hz), 3.73 (3H, s), 3.80
(3H, s), 3.81 (3H, s), 3.90 (1H, q, J = 6.7 Hz), 5.64 (1H, dd,
J = 15.7 Hz, 7.2 Hz), 6.60 (1H, d, J = 8.6 Hz), 6.63 (1H, S), 6.91 (2H,
d, J = 8.4 Hz), 7.22 (2H, d, J = 8.4 Hz), 7.50, 7.56 (2H, s), 7.62 (1H, d,
J = 8.6 Hz), 7.90, 7.96 (2H, d, J = 8.1 Hz), 8.00, 8.07 (2H, d,
J = 8.1 Hz); 13C NMR (176 MHz, DMSO‑d6): δ 45.21, 55.55, 55.95,
56.29, 59.99, 99.11, 106.76, 112.78, 114.56, 125.47, 126.36, 127.26,
128.67, 130.41, 130.54, 134.79, 138.40, 145.89, 155.53, 158.93,
160.05, 163.04, 164.30; C25H25N3O6S: m/z (495.5).
4.1.1.9. 4-(5-(3,4-Methylenedioxyphenyl)-3-phenyl-4,5-dihydro-1H-
pyrazole-1-carbonyl)benzenesulfonamide (26). M.P. 322–324 °C, 65%
yield (CH3CH2OH); IR (KBr, cm−1) ν: 3321, 3218 (NH2), 1675 (C]
O), 1618 (C]N), 1335, 1161 (O]S]O); 1H NMR (500 MHz,
DMSO‑d6):
δ 3.22 (1H, dd, J = 18.1 Hz, 4.9 Hz), 3.91 (1H, q,
J = 6.3 Hz), 5.72 (1H, dd, J = 16.5 Hz, 6.7 Hz), 6.00 (2H, s), 6.83
(1H, d, J = 7.9 Hz), 6.89 (2H, d, J = 7.8 Hz), 7.44–7.48 (3H, m), 7.53
(2H, s), 7.72 (2H, dd, J = 7.5 Hz, 1.7 Hz), 7.94, 7.97 (2H, d, J = 8.3 Hz,
8.4 Hz), 8.02, 8.09 (2H, d, J = 8.3 Hz, 8.4 Hz); 13C NMR (125 MHz,
DMSO‑d6): δ 42.18, 60.90, 101.56, 106.71, 108.88, 119.52, 126.37,
127.36, 128.66, 129.33, 130.45, 131.09, 131.34, 136.45, 138.22,
146.16, 147.02, 148.10, 156.53, 164.90; C23H19N3O5S: m/z (449.4).
4.1.1.15. 4-(3-(2,4-Dimethoxyphenyl)-5-(3,4-dimethoxyphenyl)-4,5-dihydro-
1H-pyrazole-1-carbonyl)benzenesulfonamide (32). M.P. 274–276 °C, 85%
yield (CH3OH); IR (KBr, cm−1) ν: 3313, 3214 (NH2), 1685 (C]O), 1625
(C]N), 1340, 1139 (O]S]O); 1H NMR (700 MHz, DMSO‑d6): δ 3.19 (1H,
d, J = 18.3 Hz), 3.73 (3H, s), 3.75 (3H, s), 3.81 (3H, s), 3.82 (3H, s), 3.90
(1H, q, J = 9.8 Hz), 5.65 (1H, d, J = 11.0 Hz), 6.60 (1H, d, J = 8.0 Hz),
6.65 (1H, s), 6.79 (1H, d, J = 7.1 Hz), 6.92 (2H, d, J = 11.1 Hz), 7.51, 7.57
(2H, s), 7.63 (1H, d, J = 7.9 Hz), 7.92, 7.98 (2H, d, J = 6.8 Hz, 7.0 Hz),
8.03, 8.09 (2H, d, J = 6.4 Hz, 6.5 Hz); 13C NMR (176 MHz, DMSO‑d6): δ
45.28, 55.95, 56.30, 60.28, 60.83, 99.13, 106.75, 110.01, 112.49, 112.85,
117.55, 125.51, 126.37, 128.68, 130.41, 130.52, 135.23, 138.46, 145.95,
148.46, 149.29, 155.47, 160.04, 163.02, 164.37; C26H27N3O7S: m/z
(525.5).
4.1.1.10. 4-(5-(2-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-
carbonyl)benzenesulfonamide (27). M.P. 338–340 °C, 79% yield
(CH3OH); IR (KBr, cm−1) ν: 3351, 3261 (NH2), 1688 (C]O), 1627
(C]N), 1333, 1166 (O]S]O); 1H NMR (700 MHz, DMSO‑d6): δ 3.17
(1H, d, J = 17.3 Hz), 3.79 (3H, s), 3.96 (1H, q, J = 6.0 Hz), 5.77 (1H, d,
J = 10.1 Hz), 7.00 (2H, d, J = 8.1 Hz), 7.27–7.32 (3H, m), 7.38 (2H, d,
J = 7.5 Hz), 7.52, 7.56 (2H, s), 7.66 (2H, d, J = 8.0 Hz), 7.93, 7.97 (2H,
d, J = 7.5, 7.9 Hz), 8.01, 8.07 (2H, d, J = 7.5, 7.8 Hz); C23H21N3O4S:
m/z (435.4).
4.1.1.11. 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-
carbonyl)benzenesulfonamide (28). M.P. 286–288 °C, 87% yield
(CH3OH); IR (KBr, cm−1) ν: 3319, 3208 (NH2), 1670 (C]O), 1621
(C]N), 1339, 1155 (O]S]O); 1H NMR (700 MHz, DMSO‑d6): δ 3.17
(1H, d, J = 17.3 Hz), 3.79 (3H, s), 3.96 (1H, q, J = 6.0 Hz), 5.77 (1H, d,
J = 10.1 Hz), 7.00 (2H, d, J = 8.1 Hz), 7.27–7.32 (3H, m), 7.38 (2H, d,
J = 7.5 Hz), 7.52, 7.56 (2H, s), 7.66 (2H, d, J = 8.0 Hz), 7.93, 7.97 (2H,
d, J = 7.5, 7.9 Hz), 8.01, 8.07 (2H, d, J = 7.5, 7.8 Hz); 13C NMR
(176 MHz, DMSO‑d6): δ 42.28, 55.83, 60.90, 114.75, 123.69, 125.58,
125.98, 126.37, 127.89, 128.68, 129.05, 129.29, 130.35, 135.77,
138.29, 142.54, 145.99, 147.31, 156.37, 161.63, 164.62, 165.41;
4.1.1.16. 4-(3-(3,4-Dimethoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-
dihydro-1H-pyrazole-1-carbonyl)benzenesulfonamide (33). M.P. 280–282 °C,
79% yield (CH3OH); IR (KBr, cm−1) ν: 3312, 3208 (NH2), 1653 (C]O),
1615 (C]N), 1341, 1161 (O]S]O); 1H NMR (700 MHz, DMSO‑d6): δ
3.28 (1H, d, J = 17.9 Hz, 4.7 Hz), 3.64 (3H, s), 3.75 (6H, s), 3.78 (3H, s),
3.80 (3H, s), 3.88 (1H, q, J = 9.8 Hz), 5.73 (1H, d, J = 11.4 Hz, 4.8 Hz),
6.60 (2H, s), 7.02 (1H, d, J = 8.3 Hz), 7.26 (1H, s), 7.29 (1H, d,
J = 8.3 Hz), 7.53 (2H, s), 7.95 (2H, d, J = 7.8 Hz), 8.07 (2H, d,
J = 7.8 Hz); 13C NMR (176 MHz, DMSO‑d6): δ 42.36, 55.96, 56.08,
56.33, 60.39, 61.17, 102.91, 110.23, 112.02, 121.00, 123.86, 125.61,
130.47, 136.99, 138.26, 138.33, 146.13, 149.14, 151.45, 153.62, 156.56,
164.64; C27H29N3O8S: m/z (555.6).
C
23H21N3O4S: m/z (435.5).
4.1.1.12. 4-(3,5-Bis(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-
carbonyl)benzenesulfonamide (29). M.P. 290–292 °C, 84% yield
(CH3OH); IR (KBr, cm−1) ν: 3323, 3210 (NH2), 1665 (C]O), 1627
(C]N), 1340, 1156 (O]S ]O); 1H NMR (700 MHz, DMSO‑d6): δ 3.18
(1H, d, J = 17.7 Hz), 3.74 (3H, s), 3.80 (3H, s), 3.96 (1H, q,
J = 6.1 Hz), 5.72 (1H, d, J = 10.8 Hz), 6.93 (2H, d, J = 7.5 Hz), 7.01
(2H, d, J = 7.6 Hz), 7.25 (2H, d, J = 7.5 Hz), 7.52 (2H, s), 7.67 (2H, d,
J = 7.7 Hz), 7.93 (2H, d, J = 7.5 Hz), 7.99 (2H, d, J = 7.5 Hz); 13C
NMR (176 MHz, DMSO‑d6): δ 42.18, 55.56, 55.83, 60.39, 114.56,
114.73, 123.81, 125.56, 127.42, 129.02, 130.33, 134.61, 138.39,
146.00, 156.30, 158.99, 161.59, 164.49; C24H23N3O5S: m/z (465.5).
4.2. Carbonic anhydrase inhibition
The SX.18MV-R stopped-flow instrument (Applied Photophysics,
Oxford, UK) was used to assay the inhibition of various CA isozymes,
using previously reported methods [30,54].
Acknowledgments
The authors extend their appreciation to the Deanship of Scientific
Research at King Saud University for funding the work through the
research group project No. RG-1435-046.
4.1.1.13. 4-(3-(2,4-Dimethoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-
1-carbonyl)benzenesulfonamide (30). M.P. 254–256 °C, 81% yield
(CH3OH); IR (KBr, cm−1) ν: 3331, 3209 (NH2), 1675 (C]O), 1618
(C]N), 1338, 1159 (O]S]O); 1H NMR (700 MHz, DMSO‑d6): δ 3.17
(1H, dd, J = 18.4 Hz, 4.5 Hz), 3.80 (3H, s), 3.81 (3H, s), 3.95 (1H, q,
J = 6.7 Hz), 5.70 (1H, dd, J = 16.1 Hz, 7.0 Hz), 6.61 (1H, dd,
J = 8.7 Hz, 2.1 Hz), 6.64 (1H, d, J = 2.1 Hz), 7.29 (3H, q,
J = 7.5 Hz), 7.37 (2H, t, J = 7.5 Hz), 7.51, 7.56 (2H, s), 7.65 (1H, d,
J = 8.6 Hz), 7.92, 7.98 (2H, d, J = 8.3 Hz), 8.04, 8.08 (2H, d,
J = 8.3 Hz); 13C NMR (176 MHz, DMSO‑d6): δ 45.29, 55.96, 56.30,
60.52, 99.12, 106.79, 112.70, 125.49, 125.90, 126.37, 127.78, 128.68,
Appendix A. Supplementary material
Supplementary data to this article can be found online at https://
References
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