Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors.
Cathepsin D, a lysosomal aspartyl protease, has been implicated in the pathology of Alzheimer's disease as well as breast and ovarian cancer. A weakly active cathepsin D inhibitor was identified by high throughput screening. Subsequent optimization led to the discovery of a new class of small molecule inhibitors of this enzyme, culminating with the sulfonamide 13 (IC50 = 250 nM).
Dumas
J
J
Department of Chemistry Research, Bayer Corporation, West Haven, CT 06516, USA.
Brittelli
D
D
Chen
J
J
Dixon
B
B
Hatoum-Mokdad
H
H
König
G
G
Sibley
R
R
Witowsky
J
J
Wong
S
S
D002402:Cathepsin D / Q000037:antagonists & inhibitors*; D006801:Humans; D008099:Liver / Q000201:enzymology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; D002402:Cathepsin D