Minimizing metabolic activation, drug approaches

Approaches for Minimizing Metabolic Activation of New Drug Candidates in Drug Discovery... 

Kumar S, Mitra K, Kassahun K, Badlie TA. Approaches for minimizing metabolic activation of new drug candidates in drug discovery. Handb Exp Pharmacol 2010 (196) 511-544. 

This approach to the design of structures that mimic the diuretic activity of the mercurials has led to the extremely potent compounds that lack certain of the disadvantages of the mercury-containing drugs and may share, in part, a common mechanism of action. However, other desirable attributes of the mercurials have not been reproduced. Ethacrynic acid, the only compound that has had extensive study both in animals and in man, causes potassium loss and uric acid retention and perhaps some disturbance of glucose metabolism although this latter effect appears to be minimal compared to that observed with many diuretics of the sulfonamide class. 

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