2. Academic Validation
  3. Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators

Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators

  • J Med Chem. 2006 Dec 28;49(26):7588-91. doi: 10.1021/jm0610200.
Rajeshwar Narlawar 1,  Blanca I Pérez Revuelta,  Christian Haass,  Harald Steiner,  Boris Schmidt,  Karlheinz Baumann
Affiliations

Affiliation

  • 1 Clemens Schöpf-Institute of Chemistry and Biochemistry, Darmstadt University of Technology, Petersenstrasse 22, D-64287 Darmstadt, Germany.
PMID: 17181139 DOI: 10.1021/jm0610200
Abstract

N-sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 Inhibitor carprofen into a potent gamma-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of Abeta42 and an increase of Abeta38. The most active compounds displayed activities in the low micromolar range and no effect on the gamma-secretase cleavage at the e-site.

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