title: Discovery of sulfonamide-pyrazole gamma-secretase inhibitors.
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.
authors.affiliation: Elan Pharmaceuticals, 800 Gateway Blvd., South San Francisco, CA 94080, United States.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Mattson
authors.forename: Martin L
authors.initials: ML
authors.lastname: Neitzel
authors.forename: David A
authors.initials: DA
authors.lastname: Quincy
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Semko
authors.forename: Albert W
authors.initials: AW
authors.lastname: Garofalo
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Keim
authors.forename: Andrei W
authors.initials: AW
authors.lastname: Konradi
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pleiss
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Brigham
authors.forename: Erich G
authors.initials: EG
authors.lastname: Goldbach
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.forename: John-Michael
authors.initials: JM
authors.lastname: Sauer
authors.forename: Guriqbal S
authors.initials: GS
authors.lastname: Basi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; C031280:pyrazole; D053829:Amyloid Precursor Protein Secretases