Ring-deactivated hydroxyalkylpyrrole-based inhibitors of alpha-chymotrypsin: synthesis and mechanism of action

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2003

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Martyn, D.
Vernall, A.
Clark, B.
Abell, A.

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Organic and Biomolecular Chemistry, 2003; 1(12):2103-2110

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13C NMR and mass spectrometry studies have been used to demonstrate that the inhibition of alpha-chymotrypsin by N-sulfonylhydroxymethylpyrrole inhibitors (10) is non-covalent. Hydroxyalkylpyrroles in which an electron-withdrawing group (acyl substituent) is introduced at the alternative C2 position have been synthesised and also shown to inactivate alpha-chymotrypsin. SAR studies on this class suggests that the incorporation of phenylalanine at C2 is favoured, however, there is little gain in introducing a hydrophobic substituent at C5.

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