Soft drug approach

N. Bodor, Designing safer drugs based on the soft drug approach, Trends Pharmacol. Sci. 3 53 (1982). 

N. Bodor, The application of soft drug approaches to the design of safer corticosteroids, Topical Corticosteroid Therapy A Novel Approach to Safer Drugs (E. Christophers, A. M. Kligman, E. Schopf, and R. B. Stoughton, eds.) Raven Press Ltd, New York, 1988, p. 13. 

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). 

Further improvement was obtained by using the corresponding ester analogues of methscopolamine (e.g., 7), some of them proved more potent than the similar soft methatropine analogues [79]. The ethyl ester analogue was shorter acting than even tropicamide, and, consistent with the soft drug approach, the untreated eye did not show any mydriasis, as opposed to administration of methscopolamine. 

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