Carbonic anhydrase inhibitors amination

In 1992, Goodwin and Lynn reported the first example of template-directed synthesis of DNA analogs via formation of a reversible imino linkage [21]. Five years later, Hue and Lehn described the first use of the reaction of imine condensation for the selection, by DCC, of carbonic anhydrase inhibitors from a library of amines and aldehydes [8], Upon addition of the enzyme, the formation of one library component was strongly amplified when compared to a similar reaction carried out in the absence of template. Since then, imine exchange reaction has been applied... 

CARBONIC ANHYDRASE INHIBITORS ANTIBIOTICS-METHEN AMINE 1 efficacy of methenamine Methenamine is only effective at a low pH raising the urinary pH 1 its effect Avoid co-administration... 

Scheme 5.2 Identification of carbonic anhydrase inhibitor by dynamic reductive amination.

A practical application for the casting approach was demonstrated in 1997 by Lehn and Hue, who developed an inhibitor for carbonic anhydrase II (a zinc-based metalloenzyme responsible for the conversion of CO2 to HC03 and H+, cf. Section 11.3.2). The process is based on the Schiff base imine forming reaction of an aldehyde and an amine, a process which is reversible under physiological... 

The DCCA CL concept was presented in detail and implemented through a casting process involving the recognition-induced assembly of inhibitors of the enzyme carbonic anhydrase [13]. In this study, it was found that the reversible recombination of structural fragments bearing aldehyde and amine groups into a library of imines (Fig. 5) led to a shift of the equilibrium population towards that imine product that was closest in structure to a known... 

Fig. 5. A dynamic combinatorial library of imines generated by reversible combination of a set of aldehydes and of amines. One member of the library (bottom right comer) has features close to those of a strong inhibitor of carbonic anhydrase.

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