Synthesis of potent inhibitors of histidinol dehydrogenase

Article abstract of DOI:10.1016/0960-894X(96)00384-8

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 nucleophile was a considerably weaker inhibitor (IC₅₀ ~ 20 μM).