Fig. 13.

Structures of representative inhibitors targeting the catalytic site of mACs. Pharmacological data for competitive inhibitors are listed in Table 6, and pharmacological data for noncompetitive P-site inhibitors are listed in Table 7. The (M)ANT group can spontaneously isomerize between the 2′- and 3′-ribosyl position, provided that there is only substituent and a free hydroxyl group. The different bases (A, adenine; G, guanine; I, hypoxanthine; X, xanthine; C, cytosine; U, uracil) constitute substituent Y at the ribosyl moiety. The different phosphate chains (mono-, di-, and triphosphate and hydrolysis-resistant phosphorothioates or β,γ-imidophosphates) constitute substituent X at the ribosyl moiety. (M)ANT- and TNP-nucleotides do not cross the plasma membrane and can only be used in cell-free systems or in electrophysiological studies in which compounds are injected into the cell via the patch pipette. Experimental problems with the membrane-permeable P-site inhibitors are the relatively low potency, insufficient selectivity and high lipophilicity, requiring the use of high concentrations of organic solvents.