1.
Bioorg Med Chem Lett
; 20(7): 2148-50, 2010 Apr 01.
Article
in English
| MEDLINE
| ID: mdl-20206516
ABSTRACT
Utilizing a pharmacophore hypothesis, previously described gamma-secretase inhibiting HTS hits were evolved into novel tricyclic sulfonamide-pyrazoles, with high in vitro potency, good brain penetration, low metabolic stability, and high clearance.
Subject(s)
Alzheimer Disease/drug therapy , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/metabolism , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Animals , Crystallography, X-Ray , Humans , Inhibitory Concentration 50 , Models, Molecular , Pyrazoles/chemistry , Pyrazoles/pharmacokinetics , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Sulfonamides/chemistry , Sulfonamides/pharmacokinetics
2.
Bioorg Med Chem Lett
; 12(21): 3051-3, 2002 Nov 04.
Article
in English
| MEDLINE
| ID: mdl-12372499
ABSTRACT
Potent, small molecule A beta inhibitors have been prepared that incorporate an alanine core bracketed by an N-terminal arylacetyl group and various C-terminal amino alcohols. The compounds exhibit stereospecific inhibition as demonstrated in an in vitro assay.