In conclusion, we synthetized and investigated two novel series of chromene-containing aromatic sulfonamides for their effective inhibition against different and most relevant human carbonic anhydrase isoforms such as the ubiquitous hCA I, hCA II, and the tumor associate isoforms hCA IX and XII, which are involved in a variety of diseases such as glaucoma, retinitis pigmentosa, epilepsy, and tumors. Here, CYP24A1 is linked to glaucoma.