Drug multi-component

Weber, L. (2002) Multi-Component Reactions and Evolutionary Chemistry. Drug Discovery Today, 7, 143-147. 

Weber, L. (2002) The Application of Multi-Component Reactions in Drug Discovery. Current Medicinal Chemistry, 9, 1241-1253. 

There is a wide range of treatment options provided by the social services and/or medical agencies. The most successful approaches are multi-component. They involve a psychosocial element to increase the appropriate life skills and a drug component to handle the immediate problems of drug withdrawal. Counselling and other behavioural therapies are useful components of most treatment programmes (Epstein et al., 2003). 

The past two decades have produced a revival of interest in the synthesis of polyanhydrides for biomedical applications. These materials offer a unique combination of properties that includes hydrolytically labile backbone, hydrophobic bulk, and very flexible chemistry that can be combined with other functional groups to develop polymers with novel physical and chemical properties. This combination of properties leads to erosion kinetics that is primarily surface eroding and offers the potential to stabilize macromolecular drugs and extend release profiles from days to years. The microstructural characteristics and inhomogeneities of multi-component systems offer an additional dimension of drug release kinetics that can be exploited to tailor drug release profiles. 

Domino reactions increasingly gain importance in the search for new drugs. Especially appropriate is the use of multi-component reactions in solution combinatorial chemistry. In such a process described by Wessel et al.1231 an alkoxy-nitroenone 48 was treated with different anilines 49 to give ketene-NO-acetals which in the presence of aromatic aldehydes and TfOH are transformed into 50 (scheme 10). The substrate 48 is readily available by oxidation of the nitrosugar 47. 

Hulme C, Gore V (2003) Multi-component reactions emerging chemistry in drug discover. From xylocain to crixivan. Curr Med Chem 10 51-80... 

In addition to isocyanide-based MCRs, a wealth of highly functionalized heterocycles can be obtained from 1,3-dicarbonyl, cyanomalonate and malononitrile based MCRs [19]. These easily accessible starting materials participate in a variety of multi-component reactions and have found numerous applications in drug discovery. 

Wink, M. (2008b) Evolutionary advantage and molecular modes of action of multi-component mixtures used in phytomedicine. Curr. Drug Metab., 9, 996-1009. 

Hulme, C., Nixey, T. Rapid assembly of molecular diversity via exploitation of isocyanide-based multi-component reactions. Current Opinion in Drug Discovery Development 2003, 6, 921 -929. 

Figure 8.15. A chromatogram of a cocktail of two API and some potential impurities for an impurity method of a multi-component drug product. This method uses high-pH mobile phase.

Analgesic and antiinflammatory drugs Analgesics Salicylic acid, aspirin, caffeine, butalbarbitone, phenacetin, p-chloro-acetanilide, in a multi-component analgesic product Partition p Bondapak C18 0.01% aqueous ammonium carbonate/ acetonitrile (60 40)... 

Multi-component reaction for the preparation of a variety of compounds in a single step is a powerful tool in combinatorial chemistry and drug discovery. Reaction of cyclohexyliso-nitrile and isobutyraldehyde in methanol in the presence of dimethy lamine hydrochloride as a weak acid catalyst produces A -cyclohexyl-a-dimethylaminoisovaleramide and the corresponding a-hydroxy compound [29] (Scheme 3.17). a-Aminoamidine is obtained as a sole product when dimethylamine is added as a nucleophile. Keung et al. [30] optimized the reaction conditions using various metal catalysts. Scandium (111) triflate was found to be the best catalyst and tolerant to a wide variety of amine and aldehyde units. 

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