Table 1. Inhibition, Permeability, and Isozyme Selectivity Ratio Data for Human CA Isozymes I, II, IX, and XII with Compounds 4a–4g and 5b–5e.
Ki (nM)b |
selectivity ratioc |
||||||||
---|---|---|---|---|---|---|---|---|---|
compd | cLogPa | CA I | CA II | CA IX | CA XII | I/IX | II/IX | I/XII | II/XII |
4a | –0.76 | 1050 | 94 | 215 | 9 | 5 | <1 | 117 | 10 |
4b | –0.51 | 1350 | 525 | 215 | 94 | 6 | 2 | 14 | 6 |
4c | –0.39 | 350 | 10 | 2 | 9 | 175 | 5 | 39 | 1 |
4d | –0.93 | 2400 | 265 | 2 | 60 | 1200 | 133 | 40 | 4 |
4e | –0.30 | 1550 | 110 | 2 | 8 | 775 | 55 | 194 | 14 |
4f | –0.01 | 9500 | 725 | 2 | 1 | 4750 | 363 | 9500 | 725 |
4g | –0.89 | >20000 | 190 | 115 | 85 | >174 | 2 | >235 | 2 |
5b | –2.65 | 9000 | 5 | 2 | 1 | 4500 | 3 | 9000 | 5 |
5c | –2.53 | 2400 | 6400 | 2 | 21 | 1200 | 3200 | 114 | 305 |
5d | –3.07 | >20000 | >20000 | 11 | 85 | >1800 | >1800 | >235 | >235 |
5e | –2.44 | 2400 | 185 | 2 | 34 | 1200 | 93 | 71 | 5 |
Calculated using ChemDraw Ultra 12.
Errors in the range of ±5% of the reported value, from three determinations.
Selectivity is determined by the ratio of Kis for CA isozyme relative to CA IX and XII.