Two groups of CAse inhibitors are 1. Heterocylic sulphonamides 2. Meta-disulphamoyl benzene derivatives
SAR of CAse Inhibitiors Two groups of CAse inhibitors are Heterocylic sulphonamides Meta-disulphamoyl benzene derivatives The C-2 sulphamoyl group is important for activity. The free sulphamolyl moiety is necessary to bind with Zn++ in the enzyme; hence, substitution of sulphamoyl group gives inactive compound. The moiety to which the sulphamoyl group is attached must be aromatic in character. The heterocyclic sulphonamides with higher partition coefficient and lowest Pka value have greatest CAse inhibitory and diuretic activites. Example—acetazolamide, methazolamide. N-alkylation with methyl group on ring Nof acetazolamide yields active compound (methazolamide). m-Disulphamoyl benzene do not have diuretic activity. Substituted m-sulphamoyl benzene exhibits diuretic activity. The unsubstituted sulphamoyl moiety is essential for the activity; any substitution leads to affect the potency of the compound. The sulphamoyl moiety can be replaced with similar electrophilic groups (e.g. carboxyl, carbamoyl) that may increase the potency of the compound. Maximum diuretic activity is obtained when 4th is substituted by Cl, Br, CF3 or NO2 group. Substitution of amino group at 6th position increases aleuronic activity, but decreases CAse inhibitor activity.1. Heterocylic sulphonamides
2. m-Disulphamoyl benzene derivatives
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