Synthesis of potent inhibitors of histidinol dehydrogenase
…, SD Lindell, MJ O'Mahony, EA Saville-Stones
文献索引：Dancer, Jane E.; Ford, Mark J.; Hamilton, Kenneth; Kilkelly, Michael; Lindell, Stephen D.; O'Mahony, Mary J.; Saville-Stones, Elizabeth A. Bioorganic and Medicinal Chemistry Letters, 1996 , vol. 6, # 17 p. 2131 - 2136
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).
