acetazolamide 3

FIGURE 3.1 Carbonic anhydrase inhibitors subjected to docking. For evaluation of the docking results, x-ray crystal structures of these inhibitors in complex with CA II are used as reference.

To date, mainly sulfonamides directly attached to an aromatic or heterocyclic ring moiety [such as acetazolamide (Figure 3.1), methazolamide, ethoxozolamide and dichlorophenamide] have been used as drugs. Most notable is their successful application in treating glaucoma, e.g., dorzolamide and brinzolamide (Figure 3.1; Martens-Lobenhoffer and Banditt 2002; Sugrue 2000; Willis et al. 2002), and their use as early diuretics (Preisig et al. 1987; Seely and Dirks 1977). Among the various other disorders that can be treated with CAIs are sleep apnea (Inoue et al. 1999; Philippi et al. 2001), gastroduodenal ulcers (Erdei et al. 1990; Puscas 1984), hydrocephalus (Carrion et al. 2001; Miner 1986), some neurological (Watling and Cairn-cross 2002) and neuromuscular (Koller et al. 2000; Osterman et al. 1985) disorders, essential tremor (Busenbark et al. 1992) and Parkinson's diseases (Cowen et al. 1997), epilepsy (Aribi and Stringer 2002; Leniger et al. 2002; Takeoka et al. 2002), COPD (Jones and Greenstone 2001), vasodilation (Pickkers et al. 2001) and cancer (Casini et al. 2002; Olive et al. 2001). However, several mechanisms of action are being pursued in most of these areas and CAIs need to compete as regards safety and efficacy. On the other hand, several CAIs suffer not only from a lack of selectivity with respect to CA isozymes but also from mixed activity profiles owing to their interaction with non-CAI mechanisms. This makes it more difficult to assess the relative interference with one mechanism of action, resulting in an overt pharmacological effect.

His-119 N


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