title: Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors.
abstract: 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).
authors.affiliation: Department of Chemistry Research, Bayer Corporation, West Haven, CT 06516, USA.
authors.forename: J
authors.initials: J
authors.lastname: Dumas
authors.forename: D
authors.initials: D
authors.lastname: Brittelli
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: B
authors.initials: B
authors.lastname: Dixon
authors.forename: H
authors.initials: H
authors.lastname: Hatoum-Mokdad
authors.forename: G
authors.initials: G
authors.lastname: König
authors.forename: R
authors.initials: R
authors.lastname: Sibley
authors.forename: J
authors.initials: J
authors.lastname: Witowsky
authors.forename: S
authors.initials: S
authors.lastname: Wong
mesh_terms: 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
chemical_list: D011480:Protease Inhibitors; D002402:Cathepsin D