Ring-deactivated hydroxyalkylpyrrole-based inhibitors of alpha-chymotrypsin: synthesis and mechanism of action.
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.
Martyn
Derek C
DC
Department of Chemistry, University of Canterbury, Christchurch, New Zealand.
Vernall
Andrea J
AJ
Clark
Bruce M
BM
Abell
Andrew D
AD
D000818:Animals; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; D002918:Chymotrypsin; C117608:alpha-chymotrypsin