- Synthesis of novel 1,2,4-triazine scaffold as FAK inhibitors with antitumor activity
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A series of 1,3,5-triazinic inhibitors of focal adhesion kinase (FAK) has recently been shown to exert antiangiogenic activity against HUVEC cells and anticancer efficacy against several cancer cell lines. In this report, we designed and synthesized a series of new compounds containing a 1,2,4-triazine core as novel scaffold for FAK inhibitors. These compounds displayed 10?7?M IC50 values, and the best one showed IC50 value of 0.23?μM against FAK enzymatic activity. Among them, several inhibitors potently inhibited the proliferation of glioblastoma (U-87MG) and colon (HCT-116) cancer cell lines. Docking of compound 10 into the active site of the FAK kinase was performed to explore its potential binding mode.
- Dao, Pascal,Lietha, Daniel,Etheve-Quelquejeu, Mélanie,Garbay, Christiane,Chen, Huixiong
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- Discovery of 1,2,4-triazine-based derivatives as novel neddylation inhibitors and anticancer activity studies against gastric cancer MGC-803 cells
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Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our
- Song, Jian,Cui, Xin-Xin,Wu, Bo-Wen,Li, Dong,Wang, Sheng-Hui,Shi, Lei,Zhu, Ting,Zhang, Yan-Bing,Zhang, Sai-Yang
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Picornaviridae and/or Flaviviridae viral infections with one or more nucleotide analogs.
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Paragraph 0309; 0409
(2018/03/06)
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- BICYCLIC COMPOUNDS
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Disclosed herein are nitrogen-containing bicyclic compounds, together with pharmaceutical compositions and methods of ameliorating and/or treating a cancer described herein with one or more of the compounds described herein.
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Page/Page column 59
(2016/12/01)
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- Synthesis of novel 3-substituted-5H-benzo[5,6][1, 4]thiazino[3,2-e][1,2,4]triazines and their 15-lipoxygenase inhibitory activity
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A new group of 3-substituted-5H-benzo[5,6][1,4]thiazino[3,2-e][1,2,4]triazines was designed, synthesized and evaluated as inhibitors of 15-lipoxygenase (15-LO), and the results were compared with those of standard ligand 4-methyl-2-(4-methylpiperazin-1-yl)pyrimido[4,5-b][1,4]benzothiazine (4-MMPB). Among the newly designed ligands, compound 9e showed the best IC50 of 15-LO inhibition (IC50?=?38?μM). The docking calculations were performed in MOE software based on the function of force-field scoring, in order to study the interaction of these new compounds and standard ligand with 15-LO. The docking study implied that these ligands have hydrogen bond interaction with the residue of active site of 15-LO.
- Mohammadi, Ali,Eshghi, Hossein,Bakavoli, Mehdi,Hadizadeh, Farzin,Moradi, Hassanali
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p. 1539 - 1547
(2016/07/06)
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- NEW BICYCLIC COMPOUNDS AS PI3-K AND MTOR INHIBITORS
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There is provided compounds of formula (I), wherein A1, A4, A4a, A5, B1, B1a, B2, B2a, B3, B3a, B4, B4a and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.
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Paragraph 0247; 0248
(2013/06/04)
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- NEW BICYCLIC COMPOUNDS AS PI3-K AND MTOR INHIBITORS
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There is provided compounds of formula (I), wherein A1, A4, A4a,A5, B1, B1a, B2, B2a, B3, B3a, B4, B4a and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.
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Page/Page column 81-82
(2011/12/02)
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- DERIVATIVES OF TRIAZINES AND URACILS, THEIR PREPARATION AND THEIR APPLICATION IN HUMAN THERAPEUTICS
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The present invention relates to derivatives of general formula I wherein : - W represents nitrogen, - R1 represents: ? a hydrogen or a linear or branched C1-C5 alkyl radical or, ? a C1-C3 alkyl radical substituted with groups such as trifluoromethyl, nitrile, hydroxy, C1-C3 alcoxy, C3-C6 alkoxyalkoxy, indolyl, thiophenyl, oxothiophenyl, C1-C3 N-alkylcarbamoyl groups or, ? a phenyl or pyridyl or naphthyl, or thiophenyl group optionally substituted with one or more groups such as halogen atoms, nitro, nitrile, trifluoromethyl, vinyl, methylsulfanyl, linear branched C1-C4 alkyl, linear or branched C1-C3 alkoxy groups, ? a C6 2-oxocycloalkyl radical - R2 represents a methyl or heptyl, - m, n are equal to 1, - V represents CH2, - X-Y represents -N- (C=O) -, -CH-O-, - Z represents a phenyl group substituted with one or more trifluoromethyl groups, halogen atoms or linear C1-C4 alkyl groups.
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(2010/04/03)
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- NOVEL TRIAZINEDIONE DERIVATIVES AS GABAB RECEPTOR MODULATORS
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The present invention provides novel compounds of formula I wherein W1, W2, W3, W4, W5, B, X1, X2, X3, X4, X5, E and L are as defined herein; invention compounds are gamma amino butyrique acid receptor-subtype B (“GABAB”) positive allosteric modulators (enhancers), which are useful to provide methods of treating or preventing diseases or disorders, including treatment of anxiety, depression, epilepsy, schizophrenia, cognitive disorders, spasticity and skeletal muscle rigidity, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cerebral palsy, neuropathic pain and craving associated with cocaine and nicotine, panic disorder, posttraumatic stress disorders, urge urinary incontinence, gastroesophageal reflux disease, transient lower oesophageal sphincter relaxations, functional gastrointestinal disorders and irritable bowel syndrome.
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Page/Page column 20; 27
(2010/02/16)
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- AZABICYCLO [3. 1. 0] HEXYL DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS
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The present invention relates to novel compounds of formula (I) or a salt thereof, wherein G is selected from a group consisting of: phenyl, a 5- or 6-membered monocyclic heteroaryl group, or a 8- to 11-membered heteroaryl bicyclic group; p is an integer
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Page/Page column 35-36
(2009/05/29)
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- 1,2,4-Triazine Derivatives, Preparation and Use Thereof in Human Therapy
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The invention concerns 3,5-dioxo-(2H,4H)-1,2,4-triazine derivatives of general formula (I), wherein: R1 and R2, identical or different, represent a branched or linear C1-C7 alkyl or alkenyl radical, a C1/s
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Page/Page column 7
(2008/12/06)
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- HIV INHIBITING 1,2,4-TRIAZIN-6-ONE DERIVATIVES
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The present invention relates to HIV replication inhibitors of formula (I) a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein ring A and ring B represent phenyl, pyridyl, pyridaz
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Page/Page column 62
(2008/06/13)
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- Compounds inhibiting the aggregation of superoxide dismutase-1
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The invention is directed to methods of inhibiting the rate at which superoxide dismutse-1 (SOD) aggregates using compounds that stabilize SOD dimers. The methods are useful in the study and therapy of amyotrophic lateral sclerosis. The invention also includes assays that can be used to identify compounds that stabilize dimers and SOD molecules that have been modified for use in these assays.
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Page/Page column 22; sheet 14
(2008/06/13)
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- 1,2,4-TRIAZINES DERIVATIVES, PREPARATION THEREOF AND USE THEREOF IN HUMAN THERAPEUTICS
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The invention relates to 3,5-dioxo-(2H,4H)-1,2,4-triazine derivatives of general formulae (I or II), in which in particular: R1 represents hydrogen, a linear or branched C1-C6 alkyl or alkoxy radical, a C5-C6 cycloalkyl radical, a phenyl (C1-C2) alkyl radical or a phenyl radical;-R2 represents hydrogen, a linear or branched Cl-C7alkyl radical, or a C1-C6 alkyl radical substituted with groups such as trifluoromethyl or phenyl;- linker represents a C2-C6 alkyl chain or -(CH2)n-O- (n = 2 to 5), - R3 represents a group of general formula below for which X = O, linker can be connected to the ortho-, meta- or para-positions of the aromatic of the group R3, R4, R5, R6, R7 and R8 represent hydrogen or fluorine, R9, Rio and R11 represent hydrogen or a linear or branched Cl-C5 alkyl group, in particular R9 and Rio represent the methyl group and R11 represents hydrogen or the ethyl group.
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Page/Page column 19
(2010/02/13)
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- HIV INHIBITING 1,2,4-TRIAZINES
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The present invention relates to HIV replication inhibitors of formula (I) as defined in the specification their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.
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- Synthesis of C-ribosyl imidazo[2,1-f][1,2,4]triazines as inhibitors of adenosine and AMP deaminases
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The 3-β-D-ribofuranoside 6 of the new imidazo[2,1-f][1,2,4]triazine 27 is isomeric and isoelectronic with the nucleoside deaminoformycin 1 which is a good inhibitor of adenosine deaminase (ADA) while its 5′-monophosphate 2 is a good inhibitor of adenosine 5′-monophosphate deaminase (AMPDA). The 6-methylsulfanyl derivative 7 of 6 is synthesized by condensation of the monocyclic 1,2,4-triazine 9 with bromo aldehyde 10, which is accompanied by cyclization to give the protected C-nucleoside 21; the 8-methylsulfanyl group of 21 is removed by replacement by hydrazine and oxidation. The 1,2,4-triazine 9 cyclizes similarly with chloroacetaldehyde or its dimethyl acetal to give 6,8-bis(methylsulfanyl)imidazo[2,1-f][1,2,4]triazine 17, which is converted into the parent heterocycle 27 by two routes, and into mono- and di-substituted derivatives (19, 20, 24, 25, 28-30) of the new ring system. Riboside 7 is an inhibitor of mammalian ADA (IC50 40 μM). The Royal Society of Chemistry 1999.
- Dudfield, Philip J.,Le, Van-Due,Lindell, Stephen D.,Rees, Charles W.
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p. 2929 - 2936
(2007/10/03)
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