Synthesis of potent inhibitors of histidinol dehydrogenase

Bioorganic & Medicinal Chemistry Letters
1996.0

Abstract

Novel inhibitors of histidinol dehydrogenase are described. The most potent inhibitors, compounds 18 (K i• = 4.4 nM) and 19 (K i• = 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 nucteophile was a considerably weaker inhibitor (ICs0 -201aM).

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