Table 1. Inhibition Data of Human CA Isoforms CA I, II, IV, and XII with Sulfonamides 1–7, 18–50 Reported Here and the Standard Sulfonamide Inhibitor Acetazolamide (AAZ) by a Stopped-Flow CO2 Hydrase Assay41.
|
KIa (nM) |
||||||||
|---|---|---|---|---|---|---|---|---|
| cmpd | n | R1 | R2 | R3 | CA I | CA II | CA IV | CA XII |
| 1 | C6H5 | 95.3 | 98.4 | 2854.4 | 65.4 | |||
| 2 | 4-NO2-C6H4 | 224.3 | 120.9 | 1685.3 | 77.4 | |||
| 3 | 4-F-C6H4 | 112.8 | 78.5 | 1196.7 | 60.1 | |||
| 4 | 2-Naph | 458.1 | 87.1 | 6248.1 | 78.6 | |||
| 5 | Fu | 68.4 | 62.8 | 1584.5 | 55.4 | |||
| 6 | CH2CN | 105.3 | 153.7 | 5547.2 | 113.2 | |||
| 7 | CH2C6H5 | 278.4 | 89.1 | 3587.4 | 104.3 | |||
| 18 | 1 | C6H5 | CH2CH3 | CH2CH3 | 786.6 | 8.3 | 4147.5 | 43.9 |
| 19 | 1 | C6H5 | CH2CH3 | CH2C6H5 | 4210.4 | 391.6 | >10000 | 82.6 |
| 20 | 1 | C6H5 | CH2C6H5 | CH2C6H5 | 865.9 | 412.3 | >10000 | 98.8 |
| 21 | 1 | C6H5 | (CH2)4CH3 | (CH2)4CH3 | 506.1 | 124.5 | >10000 | 69.4 |
| 22 | 1 | C6H5 | (CH2)5CH3 | (CH2)5CH3 | 878.7 | 237 | >10000 | 92.8 |
| 23 | 1 | C6H5 | (CH2)7CH3 | (CH2)7CH3 | 946.7 | 843.8 | >10000 | 99.4 |
| 24 | 2 | C6H5 | CH2CH3 | CH2CH3 | 184.7 | 8.9 | 3928.8 | 61.1 |
| 25 | 2 | C6H5 | CH2CH3 | CH2C6H5 | 544.3 | 79.6 | >10000 | 90.4 |
| 26 | 2 | C6H5 | CH2C6H5 | CH2C6H5 | 692.3 | 559.2 | 4640.8 | 302.5 |
| 27 | 2 | C6H5 | (CH2)4CH3 | (CH2)4CH3 | 563.6 | 522.6 | 3244.8 | 100.3 |
| 28 | 2 | C6H5 | (CH2)5CH3 | (CH2)5CH3 | 308.2 | 578.4 | 3455.4 | 77.8 |
| 29 | 2 | C6H5 | (CH2)7CH3 | (CH2)7CH3 | 209.3 | 778.8 | >10000 | 280 |
| 30 | 2 | CH2C6H5 | (CH2)5CH3 | (CH2)5CH3 | 518.4 | 780.8 | 3413.2 | 62.5 |
| 31 | 2 | Fu | (CH2)5CH3 | (CH2)5CH3 | 220.1 | 60.4 | 3153.7 | 9.7 |
| 32 | 1 | 2-Naph | (CH2)5CH3 | (CH2)5CH3 | 541.4 | 4562.9 | >10000 | 61.7 |
| 33 | 1 | CH2CN | (CH2)5CH3 | (CH2)5CH3 | 395.9 | 52.5 | 3478.3 | 8.6 |
| 34 | 1 | CH2C6H5 | (CH2)2C6H5 | (CH2)2CN | 777.3 | 368.5 | >10000 | 75.5 |
| 35 | 1 | Fu | (CH2)2C6H5 | (CH2)2CN | 300.8 | 73.2 | 457.4 | 8.7 |
| 36 | 1 | 4-F-C6H4 | (CH2)2C6H5 | (CH2)2CN | 676.4 | 133 | 4133.8 | 9.8 |
| 37 | 1 | 2-Naph | (CH2)2C6H5 | (CH2)2CN | 685 | 247.5 | 3812.9 | 64.9 |
| 38 | 1 | 4-NO2-C6H4 | (CH2)2C6H5 | (CH2)2CN | 407.5 | 264.2 | 2421.5 | 89.5 |
| 39 | 1 | CH2CN | (CH2)2C6H5 | (CH2)2CN | 61.6 | 0.7 | 726.6 | 8.9 |
| 40 | 1 | CH2C6H5 | (CH2)2C6H5 | (CH2)3NH2 | 242.4 | 367.3 | 2149.2 | 83.7 |
| 41 | 1 | Fu | (CH2)2C6H5 | (CH2)3NH2 | 246.7 | 57 | 374.1 | 42.7 |
| 42 | 1 | 4-F-C6H4 | (CH2)2C6H5 | (CH2)3NH2 | 451.4 | 30.4 | 365.3 | 0.6 |
| 43 | 1 | 2-Naph | (CH2)2C6H5 | (CH2)3NH2 | 506.7 | 5.6 | 819.2 | 10.5 |
| 44 | 1 | (CH2)2NH2 | (CH2)5CH3 | (CH2)5CH3 | 435.8 | 2924.8 | 913.9 | 32.5 |
| 45 | 1 | CH2C6H5 | (CH2)2C6H5 | (CH2)2COOH | 203.5 | 72 | 2330.5 | 29.7 |
| 46 | 1 | Fu | (CH2)2C6H5 | (CH2)2COOH | 79.5 | 2.4 | 335.5 | 7.1 |
| 47 | 1 | 4-F-C6H4 | (CH2)2C6H5 | (CH2)2COOH | 95.8 | 23.5 | 419.3 | 8.8 |
| 48 | 1 | 2-Naph | (CH2)2C6H5 | (CH2)2COOH | 197 | 72.5 | 680.6 | 6.8 |
| 49 | 1 | CH2COOH | (CH2)5CH3 | (CH2)5CH3 | 285.5 | 585.7 | 45.8 | 9.9 |
| 50 | 1 | Fu | (CH2)2C6H5 | (CH2)2CONHoleyl | 737.9 | 132 | 1807.1 | 5.5 |
| AAZ | 250 | 12 | 74 | 5.7 | ||||
a
Mean from three different assays, by a stopped-flow technique (errors were in the range of ±5–10% of the reported values). Fu = furyl; Naph = naphthyl.