- 5-Amino-3-tert-butyl-1-(4-nitrophenyl)-1H-pyrazole forms hydrogen-bonded sheets of alternating R22(20) and R66(32) rings
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Molecules of the title compound, C13H16N4O2, are linked by one N - H...O hydrogen bond [H...O = 2.47 A, N...O = 3.326 (2) A and N - H...O = 166°] and one N - H...N hydrogen bond [H...N = 2.19 A, N...N = 3.063 (2) A and N - H...N = 173°] into sheets containing alternating R22(20) and R66(32) rings, both types of which are centrosymmetric.
- Low, John N.,Cobo, Justo,Abonia, Rodrigo,Quiroga, Jairo,Glidewell, Christopher
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- Synthesis, structural characterization, and in vitro and in silico antifungal evaluation of azo-azomethine pyrazoles (Phn2 (phoh)chn(c3 n2 (ch3 )3 )phr, r = h or no2 )
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The azo-azomethine imines, R1-N=N-R2-CH=N-R3, are a class of active pharmacological ligands that have been prominent antifungal, antibacterial, and antitumor agents. In this study, four new azo-azomethines, R1 =
- Abonia, Rodrigo,Cuenú-Cabezas, Fernando,Fernandez, Dorancelly,Gómez Casta?o, Jovanny A.,Le Lagadec, Ronan,Restrepo-Acevedo, Andrés,Rocha-Roa, Cristian,Zacchino, Susana A.
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- Selective targeting of the αC and DFG-out pocket in p38 MAPK
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The p38 MAPK cascade is a key signaling pathway linked to a multitude of physiological functions and of central importance in inflammatory and autoimmune diseases. Although studied extensively, little is known about how conformation-specific inhibitors alter signaling outcomes. Here, we have explored the highly dynamic back pocket of p38 MAPK with allosteric urea fragments. However, screening against known off-targets showed that these fragments maintained the selectivity issues of their parent compound BIRB-796, while combination with the hinge-binding motif of VPC-00628 greatly enhanced inhibitor selectivity. Further efforts focused therefore on the exploration of the αC-out pocket of p38 MAPK, yielding compound 137 as a highly selective type-II inhibitor. Even though 137 is structurally related to a recent p38 type-II chemical probe, SR-318, the data presented here provide valuable insights into back-pocket interactions that are not addressed in SR-318 and it provides an alternative chemical tool with good cellular activity targeting also the p38 back pocket.
- R?hm, Sandra,Schr?der, Martin,Dwyer, Jessica E.,Widdowson, Caroline S.,Chaikuad, Apirat,Berger, Benedict-Tilman,Joerger, Andreas C.,Kr?mer, Andreas,Harbig, Jule,Dauch, Daniel,Kudolo, Mark,Laufer, Stefan,Bagley, Mark C.,Knapp, Stefan
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- Synthesis and p38 inhibitory activity of some novel substituted N,N′-diarylurea derivatives
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We have identified a novel series of substituted N,N′-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were
- Zhu, Dianxi,Xing, Qifeng,Cao, Ruiyuan,Zhao, Dongmei,Zhong, Wu
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- Design, synthesis and biological evaluation of novel substituted N,N′-diaryl ureas as potent p38 inhibitors
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A novel series of substituted N,N′-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation indicated
- Zhu, Dianxi,Li, Xingzhou,Zhong, Wu,Zhao, Dongmei
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p. 16604 - 16619
(2015/12/01)
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- Synthesis and Biological Evaluation of Chromenylurea and Chromanylurea Derivatives as Anti-TNF-a agents that Target the p38 MAPK Pathway
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A series of 1-aryl-3-(2H-chromen-5-yl)urea and 1-aryl-3-(chroman-5-yl)urea derivatives were designed, synthesized and evaluated for their inhibitory activities towards TNF-a production in lipopolysaccharide-stimulated THP-1 cells. The most active compound, 40g, inhibited TNF-a release with an IC50 value of 0.033 μM, which is equipotent to that of BIRB796 (IC50 = 0.032 μM).
- Li, Xingzhou,Zhou, Xinming,Zhang, Jing,Wang, Lili,Long, Long,Zheng, Zhibing,Li, Song,Zhong, Wu
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p. 2004 - 2028
(2014/03/21)
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- Substituted 1-(4-aminophenyl)pyrazoles and their use as anti-inflammatory agents
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1-(4-aminophenyl)pyrazoles optionally substituted on the 3- and 5-positions of the pyrazole ring and on the amino group at the 4-position of the phenyl ring are disclosed and described, which pyrazoles inhibit IL-2 production in T-lymphocytes.
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- 1-Phenyl-5-pyrazolyl ureas: Potent and selective p38 kinase inhibitors
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Inhibitors of the MAP kinase p38 are potentially useful for the treatment of arthritis and osteoporosis. Several 2,3-dichlorophenyl ureas were identified as small-molecule inhibitors of p38 by a combinatorial chemistry effort. Optimization for cellular potency led to the discovery of a new class of potent and selective p38 kinase inhibitors, exemplified by the 1-phenyl-5-pyrazolyl urea 7 (IC50 = 13 nM). (C) 2000 Elsevier Science Ltd.
- Dumas, Jacques,Hatoum-Mokdad, Holia,Sibley, Robert,Riedl, Bernd,Scott, William J.,Monahan, Mary Katherine,Lowinger, Timothy B.,Brennan, Catherine,Natero, Reina,Turner, Tiffany,Johnson, Jeffrey S.,Schoenleber, Robert,Bhargava, Ajay,Wilhelm, Scott M.,Housley, Timothy J.,Ranges, Gerald E.,Shrikhande, Alka
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p. 2051 - 2054
(2007/10/03)
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