Convergent synthesis and preliminary biological evaluations of the stilbenolignan (±)-aiphanol and various congeners

Treatment of an equimolar mixture of stilbene 7 and cinnamyl alcohol 8 with silver carbonate in acetone–benzene afforded a ca. 2 : 1 : 2 : 1 mixture of the stilbenolignan (±)-aiphanol (1) and congeners 2–4 each of which show significant anti-angiogenic and COX-2 inhibitory properties.

NSAR: Klassifizierung und Wirkspektrum: Eine heterogene Arzneistoffklasse

NSAR sind etablierte Arzneistoffe zur Behandlung entzundlicher Erkrankungen wie z.B. der rheumatoiden Arthritis, der Osteoarthritis und der Arthrose. In den letzten Jahren ist durch die Entwicklung von selektiven COX-2-Hemmstoffen der Arzneischatz bereichert worden. Allerdings gibt es immer mehr Anhaltspunkte, dass mit den selektiven COX-2-Hemmern hinsichtlich der Vertraglichkeit keine den klassischen NSAR deutlich uberlegene Substanzgruppe erhalten wurde.So mahnte die amerikanische Arzneimittelbehorde FDA den Rofecoxib (Vioxx ®)-Hersteller wegen „falscher, unausgewogener oder irrefuhrender Aussagen” ab, nachdem sich herausgestellt hatte, dass Daten zur Unvertraglichkeit in den publizierten…

Effects of Cyclooxygenase Inhibitors on Apoptotic Neuroretinal Cells

Glaucoma is characterized by a loss of retinal ganglion cells (RGC) which is associated with a decrease of visual function. Neuroprotective agents as a new therapeutic strategy could prevent the remaining neurons from apoptotic cell death. Previous studies have shown the involvement of the Cyclooxygenase (COX)-2 signalling in the apoptotic death of neurons. Herein we investigated the neuroprotective effect of COX-1/COX-2- and selective COX-2- inhibitors on apoptotic. R28, a neuroretinal cell line and determined the PGE2 levels by ELISA. Furthermore we investigated differences in protein expression in the cells after exposure to elevated pressure compared to untreated cells by ProteinChip a…

ChemInform Abstract: Investigations Concerning the COX/5-LOX Inhibiting and Hydroxyl Radical Scavenging Potencies of Novel 4,5-Diaryl Isoselenazoles.

The aim of this study was to investigate 4,5-diaryl isoselenazoles as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) which can intervene into the inflammatory processes via different mechanisms of action creating a new class of compounds. Here we describe the synthesis of COX/LOX inhibitors which additionally reduce the level of reactive oxygen species, such as hydroxyl radicals which are well known for supporting inflammation processes in Parkinson's disease, Alzheimer's disease and rheumatoid arthritis.

Investigations Concerning the Correlation of COX-1 Inhibitory and Hydroxyl Radical Scavenging Activity

The aim was to study the COX-1 inhibiting efficacy in context with hydroxyl radical scavenging properties of compounds bearing a carboxylic acid and ester function, respectively. In general, the acids are more potent radical scavengers than the corresponding esters but there is no clear correlation with their COX-1 inhibiting potencies. A feasible scavenging mechanism of carboxylic acids is discussed.

ChemInform Abstract: NSAR: Classification and Pharmacological Effects

A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.

An early step of the inflammatory response, the rolling of leukocytes on activated endothelial cells, is mediated by selectin/carbohydrate interactions. The tetrasaccharide sialy Lewisx is a ligand for E-, P-, and L-selectin and therefore serves as a lead structure for the development of analogues. A combination of synthesis and structure-based design allowed rapid optimization. The current lead 2a was evaluated in our E-selectin cell flow chamber assay where it proved to inhibit rolling and adhesion with an IC50 of 28+/-7 microM. The assays used are predictive for the in vivo efficacy of test compounds as shown for 2a in a proteose peptone induced peritonitis model of acute inflammation in…

Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles

The aim of this study was to investigate 4,5-diaryl isoselenazoles as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) which can intervene into the inflammatory processes via different mechanisms of action creating a new class of compounds. Here we describe the synthesis of COX/LOX inhibitors which additionally reduce the level of reactive oxygen species, such as hydroxyl radicals which are well known for supporting inflammation processes in Parkinson's disease, Alzheimer's disease and rheumatoid arthritis.

Diaryl-dithiolanes and -isothiazoles: COX-1/COX-2 and 5-LOX-inhibitory, OH scavenging and anti-adhesive activities

Three series of non-steroidal anti-inflammatory drugs (NSAIDs) inhibiting the cyclooxygenase/5-lipoxygenase (COX/5-LOX) pathways as such as formation of hydroxyl radicals and adhesion were prepared: 4,5-diaryl isothiazoles, 4,5-diaryl 3H-1,2-dithiole-3-thiones and 4,5-diaryl 3H-1,2-dithiole-3-ones. The aim of the present study was to develop substances which can intervene into the inflammatory processes via different mechanisms of action as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) with increased anti-inflammatory potential. The current lead 11a was evaluated in COX-1/2, 5-LOX and (*)OH scavenging in vitro assays and in a static adhesion assay where it proved to inhib…

Cyclooxygenase-1/2 (COX-1/COX-2) and 5-lipoxygenase (5-LOX) inhibitors of the 6,7-diaryl-2,3-1H-dihydropyrrolizine type

A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and RIA for COX-2. The balance between COX-1/COX-2 and 5-LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6- and 7-position of the pyrrolizine nucleus. Structure-activity relationships are discussed.