Soft drug

Soft drugs are active isosteric-isoelectronic analogues of a lead compound, but they are deactivated in a predictable and controllable way after achieving their therapeutic role [49-54]. They are designed to be rapidly metabolized into inactive species and, hence, to simplify the transformation-distribution-activity 

Since then, the following five distinct types have been identified [50, 52-54, 

soft drugs based on the inactive metabolite approach 

In soft drug design, the goal is not to avoid metabolism but rather to control and direct it. Inclusion of a metabolically sensitive spot into the drug molecule makes possible the design and the prediction of the major metabolic pathway and avoids the formation of undesired toxic, active, or high-energy 

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A different task was pursued by the CM of CsA with various maleates 339 [ 148]. The CM demanded in this case the highly active Hoveyda catalyst D, that exhibits potency not reached by the phosphine-containing catalysts C and E. Under the conditions given in Scheme 65, metathesis with maleates 339 led (E)-selectively to the a,/J-unsaturated ester derivatives 340 in high yield. Compounds 340 still demonstrated activity comparable to that of CsA and are thus potential soft drugs via esterase-mediated biotransformation to the corresponding inactive carboxylic acids 341. 

Bodor, N. Buchwald, P. (2006) Designing Safer (Soft) Drugs by Avoiding the Formation of Toxic and Oxidative Metabolites. Molecular Biotechnology, 26(2), 123-132. 

It has been suggested that MDMA and cannabis are soft drugs without many adverse effects. Do you agree (Note this question also applies to Chapter 7.)... 

Graffner-Nordberg M, Sjodin K, Tunek A, Hallberg A (1998) Synthesis and enzymatic hydrolysis of esters, constituting simple models of soft drugs. Chem Pharm Bull 46 591-601... 

N. Bodor, Novel Approaches to the Design of Safer Drugs Soft Drugs and Site-Specific Chemical Delivery Systems , in Advances in Drug Research , Ed. B. Testa, Academic Press, London, Vol. 13, 1984, p. 255-331. 

Bodor, who pioneered the concept and coined the term, has defined soft drugs as ... 

A typical example is succinylcholine (suxamethonium, 7.62), although the discovery of this agent predates by decades the concept of soft drugs. In most individuals, this curarimimetic agent is very rapidly hydrolyzed to choline by plasma cholinesterase with a tm value of ca. 4 min [76] [134],... 

Recent results suggest a promising application of soft drugs in the field of topical corticosteroids (e.g., loteprednol etabonate [142]) and calcium antagonists (e.g., clevipidine [143]). 

M. Graffner-Nordberg, K. Sjodin, A. Tunek, A. Hallberg, Synthesis and Enzymatic Hydrolysis of Esters, Constituting Simple Models of Soft Drugs , Chem. Pharm. Bull. 1998,46, 591-601. 

G. N. Kumar, R. H. Hammer, N. S. Bodor, Soft Drugs 12 Design, Syntheses and Evaluation of Soft Anticholinergics , Drug Design Discovery 1993,10, 11-21. 

H. S. Yang, W. M. Wu, N. Bodor, Soft Drugs. XX. Design, Synthesis and Evaluation of Ultra-Short Acting Beta-Blockers , Pharm. Res. 1995, 12, 329-336. 

N. Bodor, T. Loftsson, W. M. Wu, Metabolism, Distribution, and Transdermal Permeation of a Soft Corticosteroid, Loteprednol Etabonate , Pharm. Res. 1992, 9, 1275-1278 N. Bodor, W. M. Wu, T. Murakami, S. Engel, Soft Drugs 19. Pharmacokinetics, Metabolism and Excretion of a Novel Soft Corticosteroid, Loteprednol Etabonate, in Rats , Pharm. Res. 1995, 72, 875-879. 

N. Bodor (1984). Novel approaches to the design of safer drugs soft drugs and site-specific... 

Brain chemical which is important in determining mood and some of the effects of drugs. One group of antidepressants is the specific serotonergic re-uptake inhibitors See reference to hard drugs. In this distinction, soft drugs are the less addictive kinds... 

Bodor, N., and Buchwald, P. Soft drug design General principles and recent applications. Med,. Res. Rev. 20 58-101, 2000. 

Drug Targeting by Retrometabolic Design Soft Drugs and Chemical Delivery Systems... 

P. Druzgala, G. Hochhaus, and N. Bodor, Soft drugs 10 Blanching activity and receptor binding affinity of a new type of glucocorticoid Ioteprednol etabonate, J. Steroid Biochem. 38 149 (1991). 

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