- Macrocyclic glutaminase GLS1 inhibitor or pharmaceutically acceptable salt thereof and preparation method and application thereof
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The invention relates to the field of biological medicine, in particular to a series of macrocyclic glutaminase inhibitors, a synthesis method and medical application thereof, and particularly relatesto prevention or treatment of glutaminase related diseases. Meanwhile, the inventor performs a series of in-vitro anti-tumor activity evaluation on the synthesized compounds, and particularly, most of the compounds have good inhibitory activity on cancer cells.
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Paragraph 0113; 0115; 0118-0119
(2020/08/02)
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- BIS-PYRIDAZINE COMPOUNDS AND THEIR USE IN TREATING CANCER
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof, where R1 can be hydro, methoxy, difluoromethoxy or trifluoromethoxy; R2 can be hydro, methoxy, trifluoromethoxy or trifluoromethyl; and R3 can be hyd
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Page/Page column 28
(2017/07/06)
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- PYRROLIDINO HETEROCYCLES
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The invention relates to compounds of formula I wherein A1, A2, A3, B, R1, R2, R3 and R4 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used as medicaments.
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Paragraph 0407-0409
(2015/03/31)
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- Development of new highly potent imidazo[1,2-b[pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1
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Using a structure-based design approach, we have developed a new series of imidazo[1,2-b]pyridazines, targeting the calcium-dependent protein kinase-1 (CDPK1) from Toxoplasma gondii. Twenty derivatives were thus synthesized. Structure-activity relationships and docking studies confirmed the binding mode of these inhibitors within the ATP binding pocket of TgCDPK1. Two lead compounds (16a and 16f) were then identified, which were able to block TgCDPK1 enzymatic activity at low nanomolar concentrations, with a good selectivity profile against a panel of mammalian kinases. The potential of these inhibitors was confirmed in vitro on T. gondii growth, with EC50 values of 100 nM and 70 nM, respectively. These best candidates also displayed low toxicity to mammalian cells and were selected for further in vivo investigations on murine model of acute toxoplasmosis.
- Moine, Espérance,Dimier-Poisson, Isabelle,Enguehard-Gueiffier, Cécile,Logé, Cédric,Pénichon, Mélanie,Moiré, Nathalie,Delehouzé, Claire,Foll-Josselin, Beátrice,Ruchaud, Sandrine,Bach, Stéphane,Gueiffier, Alain,Debierre-Grockiego, Fran?oise,Denevault-Sabourin, Caroline
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- IMIDAZOLE DERIVATIVES
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The present invention relates to compounds of formula (I), wherein A, B, R1 and R2 are as defined herein before.
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Page/Page column 60
(2015/06/11)
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- PYRROLIDINO HETEROCYCLES
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The invention relates to compounds of formula I wherein A1, A2, A3, B, R1, R2, R3 and R4 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit PDE10A and can be used as medicaments.
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Page/Page column 58-59
(2014/01/07)
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- Synthesis and in vitro evaluation of imidazo[1,2- b ]pyridazines as ligands for β-amyloid plaques
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A series of imidazo[1,2-b]pyridazine derivatives were synthesized and evaluated for binding to amyloid plaques in vitro using synthetic aggregates of Aβ1?40. Binding affinities of these compounds were found to range from 11.0 to >1000 nM, depending on the various substitution patterns in the 6-position and 2-position. 2-(4′-Dimethylaminophenyl)-6- (methylthio)imidazo[1,2-b]pyridazine (4) showed high binding affinity (K i = 11.0 nM) and might be useful for the development of novel positron emission tomography radiotracers for imaging Aβ plaques.
- Zeng, Fanxing,Alagille, David,Tamagnan, Gilles D.,Ciliax, Brian J.,Levey, Allan I.,Goodman, Mark M.
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body text
p. 80 - 84
(2010/11/05)
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- cMET INHIBITORS
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Compounds of the following formula are provided for use with cMET: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.
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Page/Page column 134
(2010/04/03)
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- REGIOSELECTIVE PROCESS FOR PREPARING BENZIMIDAZOLE THIOPHENES
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The present invention provides a process for preparing benzimidazole thiophene compounds of formula I. Intermediates used in the process are also claimed.
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Page/Page column 243-244
(2010/11/26)
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- A new approach towards the synthesis of 3-amino-6- (hetero)arylpyridazines based on palladium catalyzed cross-coupling reactions
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The synthesis of 3-amino-6-(hetero)arylpyridazines via palladium catalyzed cross-coupling reactions (Suzuki, Stille) on 3-amino-6- chloropyridazine (1a) and 3-amino-6-iodopyridazine (1b) has been investigated. Comparison of the results shows that there is
- Maes, Bert U. W.,Lemière, Guy L. F.,Dommisse, Roger,Augustyns, Koen,Haemers, Achiel
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p. 1777 - 1781
(2007/10/03)
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- Imidazo[1,2-b]pyridazines. XXI syntheses of some 3-acylaminomethyl-6-(chloro and iodo)-2-(substituted phenyl)-imidazo[1,2-b]pyridazines and -imidazo[1,2-a]pyridines and their interaction with central and mitochondrial benzodiazepine receptors
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A series of 3-acylaminomethyl-6-(chloro, iodo and methyl)-2-(phenyl, 4′-t-butylphenyl, 4′-cyclohexyl-phenyl, biphenyl-4′-yl, 4′-chlorophenyl and 4′-iodophenyl)imidazo[1,2-b]pyridazines and imidazo[1,2-a]pyridines has been prepared and examined for interac
- Barlin, Gordon B.,Davies, Les P.,Harrison, Peter W.
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