Selective optimization of side activities

A group of compounds for which a completely unrelated side effect was observed are 4-hydroxy-pyrones and 4-hydroxy-coumarons, which are chemically closely related to anticoagulant vitamin K antagonists. Screening at Parke-Davis showed 

Drug candidates have also been derived from herbicides and fungicides. By screening the BASF library for endothelin receptor ligands, compound 96 was 

Burger, A Guide to the Chemical Basis of Drug Design, John Wiley Sons, New York 1983. 

Sneader, Drug Discovery The Evolution of Modern Medicines, John Wiley Sons, Chichester 1985. 

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Wermuth CG. (2004) Selective optimization of side activities Another way for drug discovery. /. Med. Chem. 47 1303-1314. 

In theory, a drug with poor target specificity can be modified to enhance the side effect and decrease the original effect. This process is called selective optimization of side activities (SOSA). A significant advantage to SOSA is that the molecules, now considered hits for their secondary activity, have already been studied in clinical trials. The oral... 

Wermuth, C. Selective Optimization of Side Activities Another Way for Drug Discovery. J. Med. Chem. 2004, 47, 1303-1314. 

The SOSA approach (SOSA = Selective Optimization of Side Activities) represents an original alternative to high-throughput screening (HTS) [29-31]. SOSA consists of two steps ... 

A new strategy in drug discovery, the selective optimization of side activities (the SOSA approach), has been formulated by Camille Wermuth [17,18 cf. Chapter I—1], In this approach, minor side activities of active compounds serve as the starting point for structural variations, ultimately to obtain analogues that now have the former side effect as their main activity. In this manner, nanomolar acetylcholinesterase (AChE) inhibitors as well as nanomolar muscarinic M, receptor and 5-HT3 receptor ligands could be derived from the antidepressant minaprine [17,18],... 

Selective optimization of side activities as a way for drug discovery 04JMC1303. 

Wermuth, C. G. Selective optimization of side activities the SOSA approach. Drug Discov. Today 2006, 11, 160-164. 

Ravichandran, V., Jain, P.K., and Agrawal, R.K (2007) Discovery of a new drug from old drug an overview on selective optimization of side activities. Journal of Pharmaceutical Research, 6, 178-184. 

Besides the presented methods there are a lot of other ways to generate hits in pharmaceutical industry. Methods like SOSA (selective optimization of side activities) [16] and fragment-based approaches are presented in other chapters and are therefore not discussed here. We have tried to provide an overview of the most often used - at least from our viewpoint - lead generation method in this chapter. It is the authors experience that no single lead generation method... 

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