189501-34-6Relevant academic research and scientific papers
A fluorescent target-guided Paal-Knorr reaction
Kornienko, Alexander,La Clair, James J.,Maslivetc, Vladimir,Wagh, Sachin B.
, p. 37035 - 37039 (2020/10/19)
It has become increasingly apparent that high-diversity chemical reactions play a significant role in the discovery of bioactive small molecules. Here, we describe an expanse of this paradigm, combining a ‘target-guided synthesis’ concept with Paal-Knorr chemistry applied to the preparation of fluorescent ligands for human prostaglandin-endoperoxide synthase (COX-2).
A class of pyrrole derivatives endowed with analgesic/anti-inflammatory activity
Battilocchio, Claudio,Poce, Giovanna,Alfonso, Salvatore,Porretta, Giulio Cesare,Consalvi, Sara,Sautebin, Lidia,Pace, Simona,Rossi, Antonietta,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Schenone, Silvia,Giordani, Antonio,Di Francesco, Luigia,Patrignani, Paola,Biava, Mariangela
, p. 3695 - 3701 (2013/07/25)
We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules.
Improving the solubility of a new class of antiinflammatory pharmacodynamic hybrids, that release nitric oxide and inhibit cycloxygenase-2 isoenzyme
Biava, Mariangela,Battilocchio, Claudio,Poce, Giovanna,Alfonso, Salvatore,Consalvi, Sara,Porretta, Giulio Cesare,Schenone, Silvia,Calderone, Vincenzo,Martelli, Alma,Testai, Lara,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Sautebin, Lidia,Rossi, Antonietta,Giordani, Antonio,Patrignani, Paola,Anzini, Maurizio
, p. 287 - 298 (2013/02/23)
The development of a novel class of pharmacodynamic hybrids that inhibits COX-2 isoform is reported. These molecules display enhanced nitric oxide releasing properties due to the presence of an ionisable moiety. The in vivo analgesic/anti-inflammatory activity was maintained in relation to the parent compounds.
Novel analgesic/anti-inflammatory agents: Diarylpyrrole acetic esters endowed with nitric oxide releasing properties
Biava, Mariangela,Porretta, Giulio Cesare,Poce, Giovanna,Battilocchio, Claudio,Alfonso, Salvatore,Rovini, Michele,Valenti, Salvatore,Giorgi, Gianluca,Calderone, Vincenzo,Martelli, Alma,Testai, Lara,Sautebin, Lidia,Rossi, Antonietta,Papa, Giuseppina,Ghelardini, Carla,Di Cesare Mannelli, Lorenzo,Giordani, Antonio,Anzellotti, Paola,Bruno, Annalisa,Patrignani, Paola,Anzini, Maurizio
, p. 7759 - 7771 (2012/01/03)
The design of compounds that are able to inhibit cyclooxygenase (COX) and to release nitric oxide (NO) should give rise to drugs endowed with an overall safer profile for the gastrointestinal and cardiovascular systems. Herein we report a new class of pyrrole-derived nitrooxy esters (11a-j), cyclooxygenase-2 (COX-2) selective inhibitors endowed with NO releasing properties, with the goal of generating new molecules able to both strongly inhibit this isoform and reduce the related adverse side effects. Taking into account the metabolic conversion of nitrooxy esters into corresponding alcohols, we also studied derivatives 12a-j. All compounds proved to be very potent and selective COX-2 inhibitors; nitrooxy derivatives displayed interesting ex vivo NO-dependent vasorelaxing properties. Compounds 11c, 11d, 12c, and 12d were selected for further in vivo studies that highlited good anti-inflammatory and antinociceptive activities. Finally, two selected compounds (11c and 12c) tested in human whole blood (HWB) assay proved to be preferential inhibitors of COX-2.
Novel Ester and acid derivatives of the 1,5-diarylpyrrole Scaffold as anti-inflammatory and analgesic agents. Synthesis and in vitro and in vivo biological evaluation
Biava, Mariangela,Porretta, Giulio C.,Poce, Giovanna,Battilocchio, Claudio,Manetti, Fabrizio,Botta, Maurizio,Forli, Stefano,Sautebin, Lidia,Rossi, Antonietta,Pergola, Carlo,Ghelardini, Carla,Galeotti, Nicoletta,Makovec, Francesco,Giordani, Antonio,Anzellotti, Paola,Patrignani, Paola,Anzini, Maurizio
experimental part, p. 723 - 733 (2010/07/09)
A new generation of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More recent clinical findings highlighted how the cardiovascular toxicity of coxibs could be mitigated by an appropriate COX-1 versus COX-2 selectivity. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, selective for COX-2. Here, we describe the synthesis of new1,5-diarylpyrroles along with their inhibitory effects in vitro, ex vivo, and in vivo toward COX isoenzymes and their analgesic activity. Isopropyl-2-methyl-5-[4- (methylsulfonyl)phenyl]-1-phenyl-1H-pyrrole-3-acetate (10a), a representative member of the series, was selected for pharmacokinetic and metabolic studies. 2009 American Chemical Society.
Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/ cyclooxygenase-1 selectivity
Biava, Mariangela,Porretta, Giulio Cesare,Poce, Giovanna,Supino, Sibilla,Forli, Stefano,Rovini, Michele,Cappelli, Andrea,Manetti, Fabrizio,Botta, Maurizio,Sautebin, Lidia,Rossi, Antonietta,Pergola, Carlo,Ghelardini, Carla,Vivoli, Elisa,Makovec, Francesco,Anzellotti, Paola,Patrignani, Paola,Anzini, Maurizio
, p. 5403 - 5411 (2008/03/14)
The important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain.
1,5-Diarylpyrrole-3-acetic acids and esters as novel classes of potent and highly selective cyclooxygenase-2 inhibitors
Biava, Mariangela,Porretta, Giulio Cesare,Cappelli, Andrea,Vomero, Salvatore,Manetti, Fabrizio,Botta, Maurizio,Sautebin, Lidia,Rossi, Antonietta,Makovec, Francesco,Anzini, Maurizio
, p. 3428 - 3432 (2007/10/03)
A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.
SUBSTITUTED PYRROLYL COMPOUNDS FOR THE TREATMENT OF INFLAMMATION
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Page/Page column 9, (2008/06/13)
A class of pyrrolyl derivatives is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I wherein R1, R2, R3 and R4 are as described in the specification.
Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
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, (2008/06/13)
The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) inhibitors, H antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.
Substituted pyrrolyl compounds for the treatment of inflammation
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, (2008/06/13)
A class of pyrrolyl derivatives is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I STR1 wherein R1, R2, R3 and R4 are as described in the specification.
