- Identification of Transthyretin Tetramer Kinetic Stabilizers That Are Capable of Inhibiting the Retinol-Dependent Retinol Binding Protein 4-Transthyretin Interaction: Potential Novel Therapeutics for Macular Degeneration, Transthyretin Amyloidosis, and Th
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Dissociation of transthyretin (TTR) tetramers may lead to misfolding and aggregation of proamyloidogenic monomers, which underlies TTR amyloidosis (ATTR) pathophysiology. ATTR is a progressive disease resulting from the deposition of toxic fibrils in tiss
- Cioffi, Christopher L.,Raja, Arun,Muthuraman, Parthasarathy,Jayaraman, Aravindan,Jayakumar, Srinivasan,Varadi, Andras,Racz, Boglarka,Petrukhin, Konstantin
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Read Online
- LPXH TARGETING COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF MAKING AND USING THE SAME
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LpxH targeting compounds, compositions thereof, as well as methods for for making and using the same are disclosed herein. The LpxH target compounds typically have a structure pursuant to Formula (I) and/or a salt thereof, wherein Rb is selecte
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Paragraph 0274; 0276
(2021/04/17)
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- PYRAZOLOTRIAZOLOPYRIMIDINE DERIVATIVES AS A2A RECEPTOR ANTAGONIST
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Disclosed herein is a pyrazolotriazolopyrimidine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof useful as A2A receptor antagonist, and a pharmaceutical composition comprising the same. Also disclosed herein is a method of treating cancer using the pyrazolotriazolopyrimidine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as A2A receptor antagonist.
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Paragraph 0718-0720
(2020/02/16)
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- Structure-activity relationship of sulfonyl piperazine LpxH inhibitors analyzed by an LpxE-coupled malachite green assay
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The UDP-2,3-diacylglucosamine pyrophosphatase LpxH in the Raetz pathway of lipid A biosynthesis is an essential enzyme in the vast majority of Gram-negative pathogens and an excellent novel antibiotic target. The 32P-radioautographic thin-layer chromatography assay has been widely used for analysis of LpxH activity, but it is inconvenient for evaluation of a large number of LpxH inhibitors over an extended time period. Here, we report a coupled, nonradioactive LpxH assay that utilizes the recently discovered Aquifex aeolicus lipid A 1-phosphatase LpxE for quantitative removal of the 1-phosphate from lipid X, the product of the LpxH catalysis; the released inorganic phosphate is subsequently quantified by the colorimetric malachite green assay, allowing the monitoring of the LpxH catalysis. Using such a coupled enzymatic assay, we report the biochemical characterization of a series of sulfonyl piperazine LpxH inhibitors. Our analysis establishes a preliminary structure-activity relationship for this class of compounds and reveals a pharmacophore of two aromatic rings, two hydrophobic groups, and one hydrogen-bond acceptor. We expect that our findings will facilitate the development of more effective LpxH inhibitors as potential antibacterial agents.
- Lee, Minhee,Zhao, Jinshi,Kwak, Seung-Hwa,Cho, Jae,Lee, Myungju,Gillespie, Robert A.,Kwon, Do-Yeon,Lee, Hyunji,Park, Hyun-Ju,Wu, Qinglin,Zhou, Pei,Hong, Jiyong
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p. 641 - 651
(2019/02/19)
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- TRIAZOLOPYRIDINE INHIBITORS OF MYELOPEROXIDASE
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The present invention provides compounds of Formula (I): wherein A is as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and/or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.
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Paragraph 00522
(2017/03/28)
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- Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αiIbβ3
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A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born's method was shown to be due to inhibition of fibrinogen binding to αIIbβ3. Molecular docking of RGD mimetics to αIIbβ3 receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores. The single crystal X-ray data were obtained for five mimetics.
- Krysko, Andrei A.,Samoylenko, Georgiy V.,Polishchuk, Pavel G.,Fonari, Marina S.,Kravtsov, Victor Ch.,Andronati, Sergei A.,Kabanova, Tatyana A.,Lipkowski, Janusz,Khristova, Tetiana M.,Kuz'Min, Victor E.,Kabanov, Vladimir M.,Krysko, Olga L.,Varnek, Alexandre A.
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p. 4646 - 4661
(2013/07/26)
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- Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture
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The RNA replication machinery of HCV is a multi-subunit membrane-associated complex. NS5A has emerged as an active component of HCV replicase, possibly involved in regulation of viral replication and resistance to the antiviral effect of interferon. We report here substituted piperazinyl-N-(aryl)benzamides as potent inhibitors of HCV replication exerted via modulation of the dimerization of NS5A.
- Conte, Immacolata,Giuliano, Claudio,Ercolani, Caterina,Narjes, Frank,Koch, Uwe,Rowley, Michael,Altamura, Sergio,Francesco, Raffaele De,Neddermann, Petra,Migliaccio, Giovanni,Stansfield, Ian
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scheme or table
p. 1779 - 1783
(2009/12/03)
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