A series of benzene sulfonamide compounds are identified through virtual screening. Especially the IC₅₀ of the two compounds 1 and 2 against CAIX are 2.86 and 3.11 nM, respectively. Meanwhile, the analysis of the compounds 1.and 9 with their potent inhibitions and strong selectivity for CA IX against CA II show that the sulfamate is an important group for the inhibitors of CAs and several unique special hydrophobic groups might cause the selectivity due to their clash with the residues of the CAs These inhibitors may serve as new lead compounds for further development to treat cancer.