6082-66-2Relevant articles and documents
Methods for treating neisseria gonorrhoeae infection with substituted 1,2-dihydro-2A,5,8A-triazaacenaphthylene-3,8-diones
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Page/Page column 137, (2020/07/21)
The present invention relates to methods for treating Neisseria Gonorrhoeae infection which comprises administering to a subject in need thereof novel 1,2-dihydro-2a,5,8a-triazaacenaphthylene-3,8-dione compounds: or pharmaceutically acceptable salts thereof and/or corresponding pharmaceutical compositions.
Chemical Proteomic Profiling of Bromodomains Enables the Wide-Spectrum Evaluation of Bromodomain Inhibitors in Living Cells
Li, Xin,Wu, Yizhe,Tian, Gaofei,Jiang, Yixiang,Liu, Zheng,Meng, Xianbin,Bao, Xiucong,Feng, Ling,Sun, Hongyan,Deng, Haiteng,Li, Xiang David
supporting information, p. 11497 - 11505 (2019/08/20)
Bromodomains, epigenetic "readers" of lysine acetylation marks, exist in different nuclear proteins with diverse biological functions in chromatin biology. Malfunctions of bromodomains are associated with the pathogenesis of human diseases, such as cancer. Bromodomains have therefore emerged as therapeutic targets for drug discovery. Given the high structural similarity of bromodomains, a critical step in the development of bromodomain inhibitors is the evaluation of their selectivity to avoid off-target effects. While numerous bromodomain inhibitors have been identified, new methods to evaluate the inhibitor selectivity toward endogenous bromodomains in living cells remain needed. Here we report the development of a photoaffinity probe, photo-bromosporine (photo-BS), that enables the wide-spectrum profiling of bromodomain inhibitors in living cells. Photo-BS allowed light-induced cross-linking of recombinant bromodomains and endogenous bromodomain-containing proteins (BCPs) both in vitro and in living cells. The photo-BS-induced labeling of the bromodomains was selectively competed by the corresponding bromodomain inhibitors. Proteomics analysis revealed that photo-BS captured 28 out of the 42 known BCPs from the living cells. Assessment of the two bromodomain inhibitors, bromosporine and GSK6853, resulted in the identification of known as well as previously uncharacterized bromodomain targets. Collectively, we established a chemical proteomics platform to comprehensively evaluate bromodomain inhibitors in terms of their selectivity against endogenous BCPs in living cells.
THYROID HORMONE RECEPTOR AGONISTS AND USES THEREOF
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Paragraph 00333; 00334; 00383, (2020/01/08)
Described herein are methods and compositions for the treatment of conditions, diseases, or disorders associated with thyroid hormone receptor activity. The methods and compositions disclosed herein include the use of at least one thyroid hormone receptor agonist.
Novel tricyclics (e.g., GSK945237) as potent inhibitors of bacterial type IIA topoisomerases
Miles, Timothy J.,Hennessy, Alan J.,Bax, Ben,Brooks, Gerald,Brown, Barry S.,Brown, Pamela,Cailleau, Nathalie,Chen, Dongzhao,Dabbs, Steven,Davies, David T.,Esken, Joel M.,Giordano, Ilaria,Hoover, Jennifer L.,Jones, Graham E.,Kusalakumari Sukmar, Senthill K.,Markwell, Roger E.,Minthorn, Elisabeth A.,Rittenhouse, Steve,Gwynn, Michael N.,Pearson, Neil D.
, p. 2464 - 2469 (2016/07/07)
During the course of our research on the lead optimisation of the NBTI (Novel Bacterial Type II Topoisomerase Inhibitors) class of antibacterials, we discovered a series of tricyclic compounds that showed good Gram-positive and Gram-negative potency. Herein we will discuss the various subunits that were investigated in this series and report advanced studies on compound 1 (GSK945237) which demonstrates good PK and in vivo efficacy properties.
Access to 4-alkylaminopyridazine derivatives via nitrogen-assisted regioselective pd-catalyzed reactions
Blaise, Emilie,Kümmerle, Arthur E.,Hammoud, Hassan,De Arajo-Jnior, Jo Xavier,Bihel, Frdric,Bourguignon, Jean-Jacques,Schmitt, Martine
, p. 10311 - 10322 (2015/02/19)
3-Substituted, 6-substituted, and unsymmetrical 3,6-disubstituted 4-alkylaminopyridazines were prepared from a sequence of three chemo- and regioselective reactions combining amination and palladium-catalyzed cross-coupling reactions, such as reductive dehalogenation and Suzuki-Miyaura reactions. Extension of the methodology to Sonogashira reaction yielded a novel class of 3-substituted pyrrolopyridazines.
COMBINATIONS OF MEDICAMENTS, CONTAINING PDE4-INHIBITORS AND EP4-RECEPTOR-ANTAGONISTS
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Paragraph 0236; 0237, (2013/09/26)
The present invention relates to new medicament combinations which contain in addition to one or more PDE4-inhibitors (1) at least one EP4 receptor antagonist (2), as well as the use thereof for the treatment of preferably respiratory complaints such as particularly COPD, chronic sinusitis and asthma. The invention relates in particular to those medicament combinations which contain at least one EP4 receptor antagonist (2), in addition to one or more, preferably one, PDE4 inhibitor of general formula 1 wherein X is SO or SO2, but preferably SO, and wherein R3 denotes an optionally substituted, mono- or bicyclic, unsaturated, partly saturated or saturated heterocyclic group or an optionally substituted, mono- or bicyclic heteroaryland wherein R1 and R2 have the meanings given in claim 1, the preparation thereof and the use thereof for the treatment of respiratory complaints.
DRUG COMBINATIONS CONTAINING PDE4 INHIBITORS AND NSAIDS
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, (2012/02/06)
The present invention relates to new drug combinations which contain in addition to one or more PDE4-inhibitors at least one NSAID (=non-steroidal anti-inflammatory drug) (2), processes for preparing them and their use in treating in particular respiratory complaints such as for example COPD, chronic sinusitis and asthma. The invention particularly relates to those drug combinations which, in addition to one or more, preferably one PDE4 inhibitor of general formula 1 wherein X is SO or SO2, but preferably SO, and wherein R3 denotes an optionally substituted, mono- or bicyclic, unsaturated, partly saturated or saturated heterocyclic group or an optionally substituted, mono- or bicyclic heteroaryl and wherein R1 and R2 have the meanings given in claim 1, contain at least one NSAID (2), the preparation thereof and the use thereof for the treatment of respiratory complaints.
Investigation of the pyrazinones as PDE5 inhibitors: Evaluation of regioisomeric projections into the solvent region
Hughes, Robert O.,Maddux, Todd,Rogier, D. Joseph,Lu, Sharon,Walker, John K.,Jacobsen, E. Jon,Rumsey, Jeanne M.,Zheng, Yi,MacInnes, Alan,Bond, Brian R.,Han, Seungil
scheme or table, p. 6348 - 6352 (2011/11/29)
We describe the design, synthesis and profiling of a novel series of PDE5 inhibitors. We take advantage of an alternate projection into the solvent region to identify compounds with excellent potency, selectivity and pharmacokinetic profiles.
HETEROCYCLE-SUBSTITUTED PIPERAZINO-DIHYDROTHIENOPYRIMIDINES
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Page/Page column 17, (2010/12/29)
The invention relates to new dihydrothienopyrimidinesulphoxides of formula 1, as well as pharmacologically acceptable salts thereof, wherein X is SO or SO2, but preferably SO, and wherein R3 denotes an optionally substituted, mono- or bicyclic, unsaturated, partially saturated or saturated heterocycle or an optionally substituted, mono- or bicyclic heteroaryl and wherein R1 and R2 have the meanings stated in claim 1, as well as pharmaceutical compositions which contain these compounds. These new dihydrothienopyrimidinesulphoxides are suitable for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system or cancers.
