26032-72-4Relevant academic research and scientific papers
Discovery and mechanism of action studies of 4,6-diphenylpyrimidine-2-carbohydrazides as utrophin modulators for the treatment of Duchenne muscular dystrophy
Vuorinen, Aini,Wilkinson, Isabel V.L.,Chatzopoulou, Maria,Edwards, Ben,Squire, Sarah E.,Fairclough, Rebecca J.,Bazan, Noelia Araujo,Milner, Josh A.,Conole, Daniel,Donald, James R.,Shah, Nandini,Willis, Nicky J.,Martínez, R. Fernando,Wilson, Francis X.,Wynne, Graham M.,Davies, Stephen G.,Davies, Kay E.,Russell, Angela J.
supporting information, (2021/05/03)
Duchenne muscular dystrophy is a fatal disease with no cure, caused by lack of the cytoskeletal protein dystrophin. Upregulation of utrophin, a dystrophin paralogue, offers a potential therapy independent of mutation type. The failure of first-in-class utrophin modulator ezutromid/SMT C1100 in Phase II clinical trials necessitates development of compounds with better efficacy, physicochemical and ADME properties and/or complementary mechanisms. We have discovered and performed a preliminary optimisation of a novel class of utrophin modulators using an improved phenotypic screen, where reporter expression is derived from the full genomic context of the utrophin promoter. We further demonstrate through target deconvolution studies, including expression analysis and chemical proteomics, that this compound series operates via a novel mechanism of action, distinct from that of ezutromid.
Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies
Soares De Melo, Candice,Singh, Vinayak,Myrick, Alissa,Simelane, Sandile B.,Taylor, Dale,Brunschwig, Christel,Lawrence, Nina,Schnappinger, Dirk,Engelhart, Curtis A.,Kumar, Anuradha,Parish, Tanya,Su, Qin,Myers, Timothy G.,Boshoff, Helena I. M.,Barry, Clifton E.,Sirgel, Frederick A.,Van Helden, Paul D.,Buchanan, Kirsteen I.,Bayliss, Tracy,Green, Simon R.,Ray, Peter C.,Wyatt, Paul G.,Basarab, Gregory S.,Eyermann, Charles J.,Chibale, Kelly,Ghorpade, Sandeep R.
supporting information, p. 719 - 740 (2021/02/03)
Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.
3,3'-((Arylmethylene)bis(4-methoxy-3,1-phenylene)) dipyridine derivatives as convenient ligands for Suzuki–Miyaura chemo- and homoselective cross-coupling reactions
Hosseini, Raziyeh,Mohammadiannejad, Kazem,Ranjbar-Karimi, Reza
, (2021/08/25)
Four novel N,N-bidentate triarylmethane-based ligands bearing β-pyridyl residues have been prepared and the catalytic activity of their in-situ generated palladium complexes were studied in the Suzuki–Miyaura cross-coupling reactions. Air and moisture stable 3,3'-((arylmethylene)bis(4-methoxy-3,1-phenylene))dipyridines L1-3 showed excellent activity in the Suzuki coupling reactions of aryl halides with aryl boronic acids under thermal and sonochemical reaction conditions. The described methodology provided good to high yields in short reaction times at ambient conditions. Moreover, it offered a straightforward way for Suzuki–Miyaura chemo- and homoselective cross-coupling of aryl halides with phenyl boronic acid. The structures of synthesized compounds were fully characterized by FT-IR, 1H-NMR, 13C-NMR, and elemental analyses. The coordination of palladium acetate to nitrogen sites of L1 was also studied using FTIR spectroscopy, EDX analysis and SEM observations. Graphic abstract: The in-situ generated Pd-complexes of N,N-bidentate ligands L1-3 are described as robust and highly effective catalytic systems for the Suzuki cross-coupling of aryl halides with aryl boronic acids under thermal and sonochemical reaction conditions.[Figure not available: see fulltext.]
Anthracene derivatives and organic light-emitting diode including the same
-
Paragraph 0169; 0201-0206, (2019/10/22)
PURPOSE: An anthracene derivative is provided to have excellent power efficiency by low voltage operation and to provide an organic electroluminescent device with excellent luminance efficiency and a long lifetime. CONSTITUTION: An anthracene derivative is represented by chemical formula 1. An organic electroluminescent device includes an anode(20); a cathode(80) opposite to the anode; and an organic layer inserted between the anode and the cathode. The organic layer is one or more layers. The organic layer includes the anthracene derivative. The organic layer includes one or more layers selected from a light emitting layer(50), a hole injection layer(30), a hole transport layer(40), a hole blocking layer, an electron transport layer(60), an electron injection layer(70), and an electron blocking layer.
TRISUBSTITUTED PYRIMIDINE COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER, RETINAL DISORDERS, AND CARDIOMYOPATHIES
-
Page/Page column 33; 34, (2018/11/26)
The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular in the treatment of
Influenza virus replication inhibitor and application thereof
-
Paragraph 0825; 1218; 1222; 1223, (2018/07/30)
The invention relates to an influenza virus replication inhibitor and application thereof, and particularly relates to a compound serving as an influenza virus replication inhibitor, a preparation method thereof, a pharmaceutical composition containing the compound, and application of the compound and the pharmaceutical composition to influenza treatment.
INHIBITORS OF INFLUENZA VIRUS REPLICATION AND USES THEREOF
-
Paragraph 00344; 00449, (2018/07/31)
Provided herein is inhibitors of influenza virus replication and uses thereof. Specifically, provided herein a novel class of compounds as inhibitors of influenza virus replication, preparation methods thereof, pharmaceutical compositions containing these compounds, and uses of these compounds and pharmaceutical compositions thereof in the treatment of influenza.
INHIBITORS OF INFLUENZA VIRUS REPLICATION, APPLICATION METHODS AND USES THEREOF
-
Paragraph 00223; 00340, (2018/03/09)
A class of compounds as inhibitors of influenza virus replication, preparation methods thereof, pharmaceutical compositions containing these compounds, and uses of these compounds and pharmaceutical compositions thereof in the treatment of influenza.
INHIBITORS OF INFLUENZA VIRUS REPLICATION AND USES THEREOF
-
Paragraph 00310, (2018/07/05)
The invention provides a class of compounds as inhibitors of influenza virus replication, preparation methods thereof, pharmaceutical compositions containing these compounds, and uses of these compounds and pharmaceutical compositions thereof in the treatment of influenza.
INHIBITORS OF INFLUENZA VIRUS REPLICATION AND USES THEREOF
-
Paragraph 00251, (2018/09/21)
The invention provides a novel class of compounds as inhibitors of influenza virus replication, preparation methods thereof, pharmaceutical compositions containing these compounds, and uses of these compounds and pharmaceutical compositions thereof in the treatment of influenza.
