Soft drugs inactive metabolite-based

Soft -blockers. Because in this class inactive metabolite-based soft drugs can be obtained by introducing the hydrolytically sensitive functionality at a flexible pharmacophore region, there is considerable freedom for structural modifications. Consequently, transport and metabolism properties can be controlled more easily. 

A hypothetical inactive metabolite-based soft drug approach proved useful in solving these problems. A first attempt to incorporate ester and carbonate moieties into structure (21) (Fig. 15.8) at the R, side-chain (R2 = —CHgOgCR, —CHgOgCOR ) produced potent analgetics, but durations of action were... 

Currently, it is the only corticosteroid approved by the FDA for use in all inflammatory and allergy-related ophthalmic disorders, including inflammation after cataract surgery, uveitis, allergic conjunctivitis, and giant papillary conjunctivitis. Loteprednol etabonate resulted from a classic inactive metabolite-based soft drug approach (103-114). 

The soft drug concept was introduced in 1976 [24] and reiterated in 1980 [30-32], Since then, five distinct types have been identified [21, 25, 27-29, 33] (1) soft analogues, (2) soft drugs based on the inactive metabolite approach, (3)... 

Figure 5. Metabolism of metoprolol (8). a well-known p-blocker. and design of soft drugs (13) based on the inactive metabolite 12. Activity, metabolism, and distribution properties can be controlled via modification of the R (or some other) substituents and via modification of the distance between the aromatic ring and the ester function (77). Esmolol (20) is an USA P-blocker already approved for intravenous clinical use. while adaprolol (16) has reached clinical trials.

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