- Methods for treating neisseria gonorrhoeae infection with substituted 1,2-dihydro-2A,5,8A-triazaacenaphthylene-3,8-diones
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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.
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Page/Page column 137
(2020/07/21)
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- Chemical Proteomic Profiling of Bromodomains Enables the Wide-Spectrum Evaluation of Bromodomain Inhibitors in Living Cells
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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.
- Li, Xin,Wu, Yizhe,Tian, Gaofei,Jiang, Yixiang,Liu, Zheng,Meng, Xianbin,Bao, Xiucong,Feng, Ling,Sun, Hongyan,Deng, Haiteng,Li, Xiang David
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supporting information
p. 11497 - 11505
(2019/08/20)
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- THYROID HORMONE RECEPTOR AGONISTS AND USES THEREOF
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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.
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Paragraph 00333; 00334; 00383
(2020/01/08)
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- Novel tricyclics (e.g., GSK945237) as potent inhibitors of bacterial type IIA topoisomerases
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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.
- 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.
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p. 2464 - 2469
(2016/07/07)
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- Access to 4-alkylaminopyridazine derivatives via nitrogen-assisted regioselective pd-catalyzed reactions
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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.
- Blaise, Emilie,Kümmerle, Arthur E.,Hammoud, Hassan,De Arajo-Jnior, Jo Xavier,Bihel, Frdric,Bourguignon, Jean-Jacques,Schmitt, Martine
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p. 10311 - 10322
(2015/02/19)
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- COMBINATIONS OF MEDICAMENTS, CONTAINING PDE4-INHIBITORS AND EP4-RECEPTOR-ANTAGONISTS
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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.
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Paragraph 0236; 0237
(2013/09/26)
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- DRUG COMBINATIONS CONTAINING PDE4 INHIBITORS AND NSAIDS
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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.
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- Investigation of the pyrazinones as PDE5 inhibitors: Evaluation of regioisomeric projections into the solvent region
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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.
- 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
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scheme or table
p. 6348 - 6352
(2011/11/29)
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- HETEROCYCLE-SUBSTITUTED PIPERAZINO-DIHYDROTHIENOPYRIMIDINES
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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.
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Page/Page column 17
(2010/12/29)
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- COMPOUNDS
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Tricyclic nitrogen containing compounds and their use as antibacterials.
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Page/Page column 16-17
(2010/04/23)
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- HETEROCYCLYC SULFONAMIDES HAVING EDG-I ANTAGONISTIC ACTIVITY
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The invention relates to chemical compounds of formula (I), (Ia) and (Ib) or pharmaceutically acceptable salts thereof, which possess Edg-1 antagonistic activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-cancer effect in a warm-blooded animal, such as man.
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Page/Page column 183
(2008/12/05)
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- PYRIDAZINYL AMINE DERIVATIVES, THE USE THEREOF IN THE PREPARATION OF PICORNA VIRUS INHIBITORS
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The present invention relates to substituted pyridazinylamine derivatives of the formula I or pharmaceutically acceptable salts or hydrates thereof, wherein the substituents are defined as in the description, their preparation process, pharmaceutical compositions comprising them, and uses of the said compounds as picorna virus inhibitors for prevention and/or treatment of diseases caused by picorna viruses.
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Page/Page column 9
(2008/06/13)
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- DERIVATIVES AND ANALOGS OF N-ETHYLQUINOLONES AND N-ETHYLAZAQUINOLONES
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Bicyclic nitrogen containing compounds and their use as antibacterials.
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Page/Page column 38-39
(2008/06/13)
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- SUBSTITUTED 1-METHYL-1H-QUINOLIN-2-ONES AND 1-METHYL-1H-1,5-NAPHTHYRIDIN-2-ONES AS ANTIBACTERIALS
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Bicyclic nitrogen containing compounds of formula (I) and their use as antibacterials.
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Page/Page column 52-53
(2008/06/13)
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- AZATRICYCLIC COMPOUNDS AND THEIR USE
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Tricyclic nitrogen containing compounds),of formula (I) or a pharmaceutically, acceptable salt, solvate and/or N-oxide thereof: and their use as antibacterials.
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Page/Page column 34
(2008/06/13)
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- TRICYCLIC NITROGEN CONTAINING HETEROCYCLES AS ANTIBACTERIAL AGENTS
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Tricyclic nitrogen containing compounds and their use as antibacterials.
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Page/Page column 31-32
(2008/12/08)
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- COMPOUNDS
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Bicyclic nitrogen containing compounds and their use as antibacterials.
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Page/Page column 54
(2008/12/08)
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- TRICYCLIC NITROGEN CONTAINING COMPOUNDS AS ANTIBACTERIAL AGENTS
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Tricyclic nitrogen containing compounds and their use as antibacterials. Z1and Z2 are independently selected from CH and N.
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Page/Page column 123
(2008/12/08)
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- PYRROLO-QUINOXALINONE DERIVATIVES AS ANTIBACTERIALS
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Tricyclic nitrogen containing compounds of the following Formula (I) and their use as antibacterials.
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Page/Page column 30
(2008/06/13)
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- HETEROCYCLIC COMPOUNDS, THEIR PREPARATION AND THEIR USE AS ANTIBACTERIALS
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Tricyclic nitrogen containing compounds of formula (I) and their use as antibacterials .
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Page/Page column 72
(2008/06/13)
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- NITROGEN-CONTAINING BICYCLIC HETEROCYCLES FOR USE AS ANTIBACTERIALS
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Cyclohexane and cyclohexene derivatives and pharmaceutically acceptable derivatives hereof useful in methods of treatment of bacterial infections in mammals, particularly man.
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Page/Page column 111
(2010/02/07)
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- Pyridotriazines and pyridopyridazines
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This invention relates to bicyclic heterocycles that inhibit cyclin-dependent kinase or tyrosine kinase enzymes, or both, and as such are useful to treat cell proliferative disorders such as angiogenesis, atherosclerosis, restenosis, and cancer as well as immunological disorders such as asthma, rheumatoid arthritis, autoimmune diabetes, and graft rejection associated with transplant surgery in mammals.
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- Synthesis of 2',3'-dideoxy- and 3'-azido-2',3'-dideoxy-pyridazine nucleosides as potential antiviral agents
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The synthesis of 4-methoxy-, 4-amino-3-chloro-, and 4-amino-1-(2,3- dideoxy-β-D-glycero-pentofuranosyl)pyridazin-6-one nucleosides, 6, 19 and 20 is described. The synthesis of 3,4-dichloropyridazin-6-one (10) was accomplished in 44% overall yield using bromomaleic anhydride (17) as the starting material. The condensation of the silylated base of 10 with the halogenose 12 in the presence of trimethylsilyl triflate as a catalyst afforded a mixture of 3,4-dichloro-1-(3,5-di-O-p-toluoyl-2-deoxy-β-D- erythro-pentofuranosyl)pyridazin-6-one (13) in 67% and its α-anomer 14 in 12% yield, respectively. A series of 3'-sulfonate esters were prepared to explore the synthesis of 3-chloro-4-hydroxy-1-(3-azido-2,3-dideoxy-β-D- erythro-pentofuranosyl)pyridazin-6-one (32) via 6,3-anhydronucleoside analogues. Compounds 15, 19 and 20 were evaluated against human immunodeficiency virus, human cytomegalovirus, and herpes simplex virus type 1 but were inactive.
- Kasnar,Wise,Kucera,Drach,Townsend
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p. 459 - 479
(2007/10/02)
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