- Piperazine squaric acid diamides, a novel class of allosteric P2X7 receptor antagonists
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The P2X7 receptor (P2X7R) stands out among the purinergic receptors due to its strong involvement in the regulation of tumor growth and metastasis formation as well as in innate immune responses and afferent signal transmission. Numerous studies have pointed out the beneficial effects of P2X7R antagonism for the treatment of a variety of cancer types, inflammatory diseases, and chronic pain. Herein we describe the development of novel P2X7R antagonists, incorporating piperazine squaric diamides as a central element. Besides improving the antagonists’ potency from pIC50 values of 5.7–7.6, ADME properties (logD7.4 value, plasma protein binding, in vitro metabolic stability) of the generated compounds were investigated and optimized to provide novel P2X7R antagonists with drug-like properties. Furthermore, docking studies revealed the antagonists binding to the allosteric binding pocket in two distinct binding poses, depending on the substitution of the central piperazine moiety.
- Budde, Thomas,Grey, Lucie,Heitman, Laura H.,Hundehege, Petra,Isaak, Andreas,Junker, Anna,Koch, Oliver,Michetti, Lucia,Patberg, Marius,Schulte, Janine,Vinnenberg, Laura,van der Horst, Cas,Füsser, Friederike,Ortiz Zacarías, Natalia V.
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- Optimization of piperazine-derived ureas privileged structures for effective –antiadenovirus agents
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In recent years, human adenovirus (HAdV) infections have shown a high clinical impact in both immunosuppressed and immunocompetent patients. The research into specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients cons
- Mazzotta, Sarah,Marrugal-Lorenzo, José Antonio,Vega-Holm, Margarita,Serna-Gallego, Ana,álvarez-Vidal, Jaime,Berastegui-Cabrera, Judith,Pérez del Palacio, José,Díaz, Caridad,Aiello, Francesca,Pachón, Jerónimo,Iglesias-Guerra, Fernando,Vega-Pérez, José Manuel,Sánchez-Céspedes, Javier
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- PIPERAZINE DERIVATIVES AS ANTIVIRAL AGENTS WITH INCREASED THERAPEUTIC ACTIVITY
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The present invention provides 2-phenylpiperazine derivatives having a benzofuran-2-yl group which contributes to increase the antiviral activity as well as, for some substituents, the CC50, giving more active and less cytotoxic compounds. Alth
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Page/Page column 21; 22
(2017/09/15)
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- New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships
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The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and struct
- Sánchez-Céspedes, Javier,Martínez-Aguado, Pablo,Vega-Holm, Margarita,Serna-Gallego, Ana,Candela, José Ignacio,Marrugal-Lorenzo, José Antonio,Pachón, Jerónimo,Iglesias-Guerra, Fernando,Vega-Pérez, José Manuel
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p. 5432 - 5448
(2016/07/06)
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- PIPERAZINE DERIVATIVES AND THE USE THEREOF AS MEDICAMENT
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The present inventions relate to substituted piperazine derivatives of general formula (I) and to the manufacture of said compounds, pharmaceutical compositions comprising a compound according to general formula (I), and the use of said compounds for the treatment of various medical conditions related to glycine transporter-1 (GlyT1).
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Page/Page column 65; 66; 67
(2015/05/05)
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- Piperazine derivatives and the use thereof as medicament
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The present inventions relate to substituted piperazine derivatives of general formula (I) and to the manufacture of said compounds, pharmaceutical compositions comprising a compound according to general formula (I), and the use of said compounds for the treatment of various medical conditions related to glycine transporter-1 (GlyT1).
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Paragraph 0302; 0303; 0304; 0305; 0306
(2015/04/21)
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- Heterocyclic derivatives as HDAC inhibitors
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This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; R1 is hydrogen, halogen, C1-C6 alkyl, C1-C6/sub
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Page/Page column 20
(2009/12/27)
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- AMIDO-THIOPHENE COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain amido-thiophene compounds that, inter alia, inhibit 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1 ). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11 β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11 β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.
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Page/Page column 141
(2009/10/22)
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- Synthesis and NK1/NK2 binding activities of a series of diacyl-substituted 2-arylpiperazines
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The synthesis and binding affinity for hNK1 and hNK2 receptors of a series of diacyl substituted 2-aryl piperazines are described. SAR evaluation led to the racemic derivative 11g as an apparent dual inhibitor. Chiral chromatographic separation of 11g led to the observation that NK1 activity was shown by one enantiomer (13a) and NK2 activity was shown by the other enantiomer (13b). X-ray crystallographic analysis of the crystalline di-BOC derivative of the NK2 active piperazine (15) showed that the 2R configuration was associated with NK2 activity. Further derivatization indicated that dual NK1/NK2 activity could be built into the 2R series.
- Blythin, David J.,Chen, Xiao,Piwinski, John J.,Shih, Neng-Yang,Shue, Ho-Jane,Anthes, John C.,McPhail, Andrew T.
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p. 3161 - 3165
(2007/10/03)
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