104765-64-2Relevant articles and documents
Arylpyrrolizines as inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) or as dual inhibitors of mPGES-1 and 5-lipoxygenase (5-LOX)
Liedtke, Andy J.,Keck, Peter R. W. E. F.,Lehmann, Frank,Koeberle, Andreas,Werz, Oliver,Laufer, Stefan A.
scheme or table, p. 4968 - 4972 (2010/03/03)
We synthesized and evaluated inhibitors for the microsomal prostaglandin E2 synthase-1 (mPGES-1), based on the arylpyrrolizine scaffold. In a cell free mPGES-1 assay several "sulfonimides" exceeded our leadML3000 (3) in potency. The most promising compound, the tolylsulfonimide 11f, revealed an IC50 of 2.1 μM and is equipotent to the literature reference molecule MK886 (1). Selected compounds also potently reduced 5-LOX product formation in intact cells. Inhibition of isolated COX was occasionally remarkably cut down.
(6,7-Diaryldihydropyrrolizin-5-yl)acetic Acids, a Novel Class of Potent Dual Inhibitors of Both Cyclooxygenase and 5-Lipoxygenase
Laufer, Stefan A.,Augustin, Jan,Dannhardt, Gerd,Kiefer, Werner
, p. 1894 - 1897 (2007/10/02)
A novel class of nonantioxidant dual inhibitors of both CO and 5-LO is described.The balance between the activity against CO and 5-LO can be shifted by modifying the substitution pattern of the phenyl moiety at the 6-position of the pyrrolizine ring.Structure-activity relationships are discussed.Compound 3e with a 4-Cl substituent (IC50 = 0.21 μM (CO); 0.18 μM (5-LO)) and 3n with a 4-OCH3 substituent (IC50 = 0.1 μM (CO); 0.24 μM (5-LO)) are the most potent and well-balanced dual inhibitors of both enzymes.The inhibition of CO was determined in a bovine thrombocyte intact cell assay and that of 5-LO using intact bovine PMNL.Compound 3e was also ivestigated in human cells.
