90327-03-0Relevant articles and documents
Discovery of New Potential Anti-Infective Compounds Based on Carbonic Anhydrase Inhibitors by Rational Target-Focused Repurposing Approaches
Annunziato, Giannamaria,Angeli, Andrea,D'Alba, Francesca,Bruno, Agostino,Pieroni, Marco,Vullo, Daniela,De Luca, Viviana,Capasso, Clemente,Supuran, Claudiu T.,Costantino, Gabriele
, p. 1904 - 1914 (2016/10/12)
In academia, compound recycling represents an alternative drug discovery strategy to identify new pharmaceutical targets from a library of chemical compounds available in house. Herein we report the application of a rational target-based drug-repurposing approach to find diverse applications for our in-house collection of compounds. The carbonic anhydrase (CA, EC 4.2.1.1) metalloenzyme superfamily was identified as a potential target of our compounds. The combination of a thoroughly validated docking screening protocol, together with in vitro assays against various CA families and isoforms, allowed us to identify two unprecedented chemotypes as CA inhibitors. The identified compounds have the capacity to preferentially bind pathogenic (bacterial/protozoan) CAs over human isoforms and represent excellent hits for further optimization in hit-to-lead campaigns.
2-Aminonicotinic acid 1-oxides are chemically stable inhibitors of quinolinic acid synthesis in the mammalian brain: A step toward new antiexcitotoxic agents
Vallerini, Gian Paolo,Amori, Laura,Beato, Claudia,Tararina, Margarita,Wang, Xiao-Dan,Schwarcz, Robert,Costantino, Gabriele
, p. 9482 - 9495 (2014/01/06)
3-Hydroxyanthranilic acid 3,4-dioxygenase (3-HAO) is the enzyme responsible for the production of the neurotoxic tryptophan metabolite quinolinic acid (QUIN). Elevated brain levels of QUIN are observed in several neurodegenerative diseases, but pharmacological investigation on its role in the pathogenesis of these conditions is difficult because only one class of substrate-analogue 3-HAO inhibitors, with poor chemical stability, has been reported so far. Here we describe the design, synthesis, and biological evaluation of a novel class of chemically stable inhibitors based on the 2-aminonicotinic acid 1-oxide nucleus. After the preliminary in vitro evaluation of newly synthesized compounds using brain tissue homogenate, we selected the most active inhibitor and showed its ability to acutely reduce the production of QUIN in the rat brain in vivo. These findings provide a novel pharmacological tool for the study of the mechanisms underlying the onset and propagation of neurodegenerative diseases.
NEW COMPOUNDS
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Page/Page column 39, (2008/06/13)
The present invention relates to new compounds of formula Ia or Ib wherein P represents a 5- or 6-membered heteroaromatic ring containing one or two heteroatoms selected independently from N, O and S of which at least one heteroatom is nitrogen; R is hydrogen; R is selected from: C1-6alkyl, cyano, halogen, (CO)OR, and CONRR; R is selected from: C1-6alkyl, cyano, nitro, (CO)OR, C1-6alkylNRR, OC2-6alkylNRR, CONRR, and (SO2)NRR; m is 0, 1, 2, 3 or 4; n is 0, 1, 2, 3 or 4; as a free base or a salt thereof, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy.
Pharmaceutical uses and synthesis of nicotinanilide-N-oxides
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, (2008/06/13)
Disclosed are nicotinanilide-N-oxide compounds, methods for their production, pharmaceutical compositions which include these compounds, and methods for their use in various therapies.
Nicotinamide N-oxides as CXCR2 antagonists
Cutshall, Neil S,Ursino, Rocky,Kucera, Kristin A.,Latham, John,Ihle, Nathan C.
, p. 1951 - 1954 (2007/10/03)
A series of nicotinamide N-oxides was synthesized and shown to be novel, potent, and selective antagonists of the CXCR2 receptor. Furthermore, these compounds showed significant functional activity against GRO-α-driven human neutrophil chemotaxis. Compounds of this class may be useful for the treatment of inflammatory, auto-immune, and allergic disorders.
