1-(5-Carboxyindol-1-yl)propan-2-one Inhibitors of Human Cytosolic Phospholipase A2α: Effect of Substituents in Position 3 of the Indole Scaffold on Inhibitory Potency, Metabolic Stability, Solubility, and Bioavailability

2010 ◽  
Vol 53 (23) ◽  
pp. 8298-8308 ◽  
Author(s):  
Stefanie Bovens ◽  
Alwine Schulze Elfringhoff ◽  
Martina Kaptur ◽  
Dirk Reinhardt ◽  
Michael Schäfers ◽  
...  
Keyword(s):  
Metabolic Stability ◽  
Inhibitory Potency ◽  
Effect Of Substituents ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α

Inhibitors of cytosolic phospholipase A2α with carbamate structure: synthesis, biological activity, metabolic stability, and bioavailability

2014 ◽  
Vol 23 (12) ◽  
pp. 5250-5262 ◽  
Author(s):  
Julian Schwarzkopf ◽  
Tom Sundermann ◽  
Martina Arnsmann ◽  
Walburga Hanekamp ◽  
Jörg Fabian ◽  
...  
Keyword(s):  
Biological Activity ◽  
Metabolic Stability ◽  
Cytosolic Phospholipase ◽  
Structure Synthesis ◽  
Cytosolic Phospholipase A2α

scholarly journals 2-Oxoester Phospholipase A2 Inhibitors with Enhanced Metabolic Stability

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 491
Author(s):  
Giorgos S. Koutoulogenis ◽  
Maroula G. Kokotou ◽  
Daiki Hayashi ◽  
Varnavas D. Mouchlis ◽  
Edward A. Dennis ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Metabolic Stability ◽  
Aliphatic Chain ◽  
Plasma Stability ◽  
Important Class ◽  
Inhibitory Potency ◽  
Methyl Group ◽  
Cytosolic Phospholipase ◽  
Phospholipase A2 Inhibitors

2-Oxoesters constitute an important class of potent and selective inhibitors of human cytosolic phospholipase A2 (GIVA cPLA2) combining an aromatic scaffold or a long aliphatic chain with a short aliphatic chain containing a free carboxylic acid. Although highly potent 2-oxoester inhibitors of GIVA cPLA2 have been developed, their rapid degradation in human plasma limits their pharmaceutical utility. In an effort to address this problem, we designed and synthesized two new 2-oxoesters introducing a methyl group either on the α-carbon to the oxoester functionality or on the carbon carrying the ester oxygen. We studied the in vitro plasma stability of both derivatives and their in vitro inhibitory activity on GIVA cPLA2. Both derivatives exhibited higher plasma stability in comparison with the unsubstituted compound and both derivatives inhibited GIVA cPLA2, however to different degrees. The 2-oxoester containing a methyl group on the α-carbon atom to the oxoester functionality exhibits enhancement of the metabolic stability and retains considerable inhibitory potency.

Investigations on the metabolic stability of cytosolic phospholipase A2α inhibitors with 1-indolylpropan-2-one structure

2013 ◽  
Vol 206 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Jörg Fabian ◽  
Walburga Hanekamp ◽  
Mélanie H. Thomas ◽  
Jean Luc Olivier ◽  
Matthias Lehr
Keyword(s):  
Metabolic Stability ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α
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