- Design, synthesis and biological evaluation of 1H-indazole derivatives as novel ASK1 inhibitors
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Apoptosis signal-regulating kinase 1 (ASK1, MAP3K5), a member of the mitogen-activated protein kinase (MAPK) signaling pathway, is involved in cell survival, differentiation, stress response, and apoptosis. ASK1 kinase inhibition has emerged as a promisin
- Hou, Shaohua,Yang, Xiping,Yang, Yuejing,Tong, Yu,Chen, Quanwei,Wan, Boheng,Wei, Ran,Lu, Tao,Chen, Yadong,Hu, Qinghua
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- A kind of benzo [d] different wicked zuozuo apperception compound and use thereof
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The invention relates to the technical field of chemical medicine, and particularly discloses a benzo[d]isoxazole compound shown as a general formula (A) and application thereof. The compound can effectively inhibit bromodomain of BET family proteins so as to block interaction between the BET family proteins and chromatin histone to adjust genetic transcription, cause changing of a downstream signal path and exert important influence on various diseases, so that the compound and a combination thereof can be used for preparing medicine for treating or preventing diseases like tumorigenesis, inflammation, viral infection, cell proliferation disorder, autoimmune diseases and septicemia.
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Paragraph 0377; 0380; 0381; 0387; 0388
(2018/06/14)
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- Synthesis and bioevaluation of 1-phenyl-pyrazole-4-carboxylic acid derivatives as potent xanthine oxidoreductase inhibitors
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A diverse library of 1-phenyl-pyrazole-4-carboxylic acid derivatives were synthesized and evaluated for their inhibitory potency against xanthine oxidoreductase (XOR) in vitro and vivo, and the structure-activity relationship (SAR) analyses were also pres
- Li, Jing,Wu, Fangping,Liu, Xingguo,Zou, Yake,Chen, Huixiong,Li, Zheng,Zhang, Lei
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- Nitrogen-substituted phenyl pyrazole xanthine oxidoreductase inhibitor and preparation and application thereof
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The invention belongs to the technical field of pharmaceutical and chemical industry and discloses nitrogen-substituted phenyl pyrazole xanthine oxidoreductase inhibitor and preparation and application thereof. The nitrogen-substituted phenyl pyrazole xan
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Paragraph 0082
(2017/07/13)
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- [1,2,4]Triazolo[4,3-a]phthalazines: Inhibitors of diverse bromodomains
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Bromodomains are gaining increasing interest as drug targets. Commercially sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines are potent inhibitors of both the BET bromodomains such as BRD4 as well as bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new series of compounds is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily. Representative compounds are active in cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP and chromatin association. The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology.
- Fedorov, Oleg,Lingard, Hannah,Wells, Chris,Monteiro, Octovia P.,Picaud, Sarah,Keates, Tracy,Yapp, Clarence,Philpott, Martin,Martin, Sarah J.,Felletar, Ildiko,Marsden, Brian D.,Filippakopoulos, Panagis,Müller, Susanne,Knapp, Stefan,Brennan, Paul E.
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p. 462 - 476
(2014/02/14)
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- Synthesis and toxicity of new ring-fused imidazo[5,4-f] benzimidazolequinones and mechanism using amine N-oxide cyclizations
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A new synthetic route to ring-fused imidazo[5,4-f]benzimidazoles is reported that can be used to access symmetrical and unsymmetrical quinone anticancer agents. Oxone in formic acid allows cyclisation of o-tert-aminoacetanilides to give ring-fused benzimi
- Fagan, Vincent,Bonham, Sarah,McArdle, Patrick,Carty, Michael P.,Aldabbagh, Fawaz
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experimental part
p. 1967 - 1975
(2012/05/31)
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- HETEROCYCLIC COMPOUNDS AND THEIR USES
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Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjogren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.
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Page/Page column 33
(2011/01/05)
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- Naphthyl and coumarinyl biarylpiperazine derivatives as highly potent human β-secretase inhibitors. Design, synthesis, and enzymatic BACE-1 and cell assays
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Twenty novel β-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinyl series were designed for their potential use in Alzheimer's disease therapy. Enzymatic and cell-based assays have been carried out. The biological results clearly demonstrate that specific substituents located at the N4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between 40 and 70 nM), Variable temperature NMR and modeling studies are consistent with the obtained biological data, since these studies confirmed that introduction at the N4-position of the piperazine ring allows productive interactions within the BACE-1 active site, which appear to be determinative for high BACE-1 inhibitory activity. These results are of particular interest since some of the new analogues belonging to the naphthyl series are almost one log more active than the best inhibitor of the similar family recently reported.
- Garino, Cédrik,Tomita, Taisuke,Pietrancosta, Nicolas,Laras, Younes,Rosas, Roselyne,Herbette, Ga?tan,Maigret, Bernard,Quéléver, Gilles,Iwatsubo, Takeshi,Kraus, Jean-Louis
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p. 4275 - 4285
(2007/10/03)
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