95499-72-2Relevant academic research and scientific papers
Exploring the fatty acid amide hydrolase and cyclooxygenase inhibitory properties of novel amide derivatives of ibuprofen
Catalanotti, Bruno,Deplano, Alessandro,Fowler, Christopher J.,Karlsson, Jessica,Moraca, Federica,Onnis, Valentina,Svensson, Mona
, p. 815 - 823 (2020/04/02)
Inhibition of fatty acid amide hydrolase (FAAH) reduces the gastrointestinal damage produced by non-steroidal anti-inflammatory agents such as sulindac and indomethacin in experimental animals, suggesting that a dual-action FAAH-cyclooxygenase (COX) inhib
COMPOSITIONS AND METHODS FOR SUBSTRATE-SELECTIVE INHIBITION OF ENDOCANNABINOID OXYGENATION
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Page/Page column 58; 61, (2014/02/15)
Methods for selectively inhibiting endocannabinoid oxygenation but not arachidonic acid oxygenation. In some embodiments, the methods include contacting a COX-2 polypeptide with an effective amount of a substrate-selective COX-2 inhibitor. Also provided are methods for elevating a local endogenous cannabinoid concentrations; methods of reducing depletion of an endogenous cannabinoid; methods for inducing analgesia; methods of providing anxiolytic therapy; methods for providing anti-depressant therapy; and compositions for performing the disclosed methods.
Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen as Novel Analgesic Candidates
Ahmadi,Naderi,Daniali,Kazemi,Aazami,Alizadeh,Nahri-Niknafs
, p. 457 - 462 (2015/09/15)
Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice of drugs that are normally used for the treatment of pain and inflammation. Ibuprofen (I) and its analogues as the most widely used NSAIDs have been synthesized in recent years. In an effort to establish new candidates with improved analgesic properties, derivatives (II-VII) with substituted aromatic as well as aliphatic moieties were synthesized in this experiment and evaluated in formalin test with rats. The results were compared to ibuprofen and control groups. Findings indicated that derivatives with new alkylphenyl rings (VI and VII) had some similar or more analgesic activities relative to the control and ibuprofen groups, respectively; which could be justified as to more alkyl and phenyl groups instead of p-isobutylphenyl moiety in I.
Direct lactonization of 2-arylacetic acids through Pd(II)-catalyzed C-H activation/C-O formation
Yang, Mingyu,Jiang, Xingyu,Shi, Wen-Juan,Zhu, Qi-Lei,Shi, Zhang-Jie
supporting information, p. 690 - 693 (2013/04/10)
Palladium-catalyzed direct lactonization of 2-arylacetic acids through a reaction sequence that includes C-H activation/C-O formation is reported. This method provides a concise and efficient pathway to synthesize fully functionalized benzofuranone derivatives, which are highly relevant to bioactive natural and synthetic products.
Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase- activating protein (FLAP)
Banoglu, Erden,Caliskan, Burcu,Luderer, Susann,Eren, Goekcen,Oezkan, Yagmur,Altenhofen, Wolfram,Weinigel, Christina,Barz, Dagmar,Gerstmeier, Jana,Pergola, Carlo,Werz, Oliver
supporting information; experimental part, p. 3728 - 3741 (2012/08/28)
Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand- and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl) ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 μM) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 μM in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents.
Substrate-selective inhibition of cyclooxygenase-2: Development and evaluation of achiral profen probes
Windsor, Matthew A.,Hermanson, Daniel J.,Kingsley, Philip J.,Xu, Shu,Crews, Brenda C.,Ho, Winnie,Keenan, Catherine M.,Banerjee, Surajit,Sharkey, Keith A.,Marnett, Lawrence J.
supporting information, p. 759 - 763 (2012/10/29)
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 μM for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.
The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer's disease modifying agent
Stock, Nicholas,Munoz, Benito,Wrigley, Jonathan D.J.,Shearman, Mark S.,Beher, Dirk,Peachey, James,Williamson, Toni L.,Bain, Gretchen,Chen, Weichao,Jiang, Xiaohui,St-Jacques, Rene,Prasit, Peppi
, p. 2219 - 2223 (2007/10/03)
The subtle modification of a selection of Aβ42 inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining Aβ42 inhibition. Methylflurbiprofen 6 exhibited similar in vitro Aβ42 inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer's disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development.
In Vivo Characterization of Hydroxamic Acid Inhibitors of 5-Lipoxygenase
Summers, James B.,Gunn, Bruce P.,Mazdiyasni, Hormoz,Goetze, Andrew M.,Young, Patrick R.,et al.
, p. 2121 - 2126 (2007/10/02)
The hydroxamic acid functionality can be incorporated into simple molecules to produce potent inhibitors of 5-lipoxygenase.The ability of many of these hydroxamates to inhibit leukotriene synthesis in vivo has been measured directly with a rat peritoneal anaphylaxis model.Despite their potent enzyme inhibitory activity in vitro, many orally dosed hydroxamic acids only weakly inhibited leukotriene synthesis in vivo.This discrepancy is attributable at least in part to the rapid metabolism of hydroxamates to the corresponding carboxylic acids, which are inactive against the enzyme.A study of the structural features that affect this metabolism revealed that 2-arylpropionohydroxamic acids are relatively resistant to metabolic hydrolysis.Several members of this class of hydroxamates are described that are orally active inhibitors of leukotriene synthesis.
