Author/Authors :
Jane E. Dancer، نويسنده , , Mark J. Ford، نويسنده , , Kenneth Hamilton، نويسنده , , Michael Kilkelly، نويسنده , , Stephen D. Lindell، نويسنده , , Mary J. OʹMahony، نويسنده , , Elizabeth A. Saville-Stones، نويسنده ,
Abstract :
Novel inhibitors of histidinol dehydrogenase are described. The most potent inhibitors, compounds 18 (Fi* = 4.4 nM) and 19 (Ki* = 2.9 nM) exploit a hitherto unreported lipophilic binding pocket adjoining the active site. Preliminary SAR data for this pocket are detailed. The electrophilic ketone 6 designed to bind to an active site nucleophile was a considerably weaker inhibitor (IC50 20μM).
