Sperberweg 15

Aachen, Germany

Sperberweg 15

Aachen, Germany
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Vidal-Torres A.,Esteve | De La Puente B.,Esteve | Rocasalbas M.,Esteve | Tourino C.,University Pompeu Fabra | And 10 more authors.
European Journal of Pharmacology | Year: 2013

While opioids are potent analgesics widely used in the management of pain, a number of well-known adverse effects limit their use. The sigma-1 receptor is a ligand-regulated molecular chaperone involved in pain processing, including modulation of opioid antinociception. However, data supporting the potential use of sigma-1 receptor ligands as suitable opioid adjuvants are based on studies that use non selective ligands. Also, safety issues derived from combination therapy are poorly addressed. In this study we used the new selective sigma-1 receptor antagonist S1RA (E-52862) to characterize the effect of selective sigma-1 receptor blockade on opioid-induced efficacy- and safety-related outcomes in mice. S1RA (40 mg/kg) had no effect in the tail-flick test but did enhance the antinociceptive potency of several opioids by a factor between 2 and 3.3. The potentiating effect of S1RA on morphine antinociception did not occur in sigma-1 receptor knockout mice, which supports the selective involvement of the sigma-1 receptor. Interestingly, S1RA co-administration restored morphine antinociception in tolerant mice and reverted the reward effects of morphine in the conditioned place preference paradigm. In addition, enhancement of antinociception was not accompanied by potentiation of other opioid-induced effects, such as the development of morphine analgesic tolerance, physical dependence, inhibition of gastrointestinal transit, or mydriasis. The use of sigma-1 receptor antagonists as opioid adjuvants could represent a promising pharmacological strategy to enhance opioid potency and, most importantly, to increase the safety margin of opioids. S1RA is currently in phase II clinical trials for the treatment of several pain conditions. © 2013 Elsevier B.V.


Chen X.Y.,RWTH Aachen | Buschmann H.,Sperberweg 15 | Bolm C.,RWTH Aachen
Synlett | Year: 2012

Sulfoximine- and sulfilimine-based diamino-diphenyl sulfone (DAPSON) analogues have been prepared and their COX-1 and COX-2 inhibition potencies as well as LTBand TNF binding properties were studied. Furthermore, their antiproliferative activities on cancer cell growth were investigated. Neither compounds showed significant bioactivities. Copyright © 2012 by Thieme Medical Publishers, Inc.


Park S.J.,RWTH Aachen | Buschmann H.,Sperberweg 15 | Bolm C.,RWTH Aachen
Bioorganic and Medicinal Chemistry Letters | Year: 2011

The syntheses and biological profiles of sulfoximine-based Vioxx® analogs 2 are described. Interesting data have been obtained for 2a, which shows a selective COX-2 inhibition (albeit not as strong as Vioxx® itself) exhibiting reduced hERG activity compare to the parent sulfone Vioxx® (1). © 2011 Elsevier Ltd. All rights reserved.


Park S.J.,RWTH Aachen | Baars H.,RWTH Aachen | Mersmann S.,RWTH Aachen | Buschmann H.,Sperberweg 15 | And 7 more authors.
ChemMedChem | Year: 2013

From insects to cancer: N-Cyano sulfoximines were evaluated for COX inhibition and antiproliferative activity against a panel of cancer cell lines. The most active compound exhibited potent COX-2 inhibition, some selectivity for COX-2 over COX-1, only slight cytotoxicity towards healthy cells (HaCaT skin cells), and no mutagenic potential (as determined by an Ames assay). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Chen X.Y.,RWTH Aachen | Park S.J.,RWTH Aachen | Buschmann H.,Sperberweg 15 | De Rosa M.,RWTH Aachen | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

Sulfoximine-based acyclic triaryl olefins 8 and 9 have been prepared and initial studies have been performed to determine their biological profiles. In contrast to their sulfonyl-substituted analog 2 sulfoximines 8 and 9 show low COX inhibitory activity. All compounds affect the estrogen receptors. While sulfone 2 interacts exclusively with ER β, sulfoximines 8 and 9 reveal almost equal blocking potencies for both estrogen receptors, ER α and ER β. In the tested series, triaryl olefin 9a shows the highest inhibitory activities with 91% and 80%, respectively (at 10 μM). © 2012 Elsevier Ltd. All rights reserved.

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