3245-94-1Relevant academic research and scientific papers
In silico identification, design and synthesis of novel piperazine-based antiviral agents targeting the hepatitis C virus helicase
Bassetto, Marcella,Leyssen, Pieter,Neyts, Johan,Yerukhimovich, Mark M.,Frick, David N.,Courtney-Smith, Matthew,Brancale, Andrea
supporting information, p. 1115 - 1131 (2016/11/09)
A structure-based virtual screening of commercial compounds was carried out on the HCV NS3 helicase structure, with the aim to identify novel inhibitors of HCV replication. Among a selection of 13 commercial structures, one compound was found to inhibit the subgenomic HCV replicon in the low micromolar range. Different series of new piperazine-based analogues were designed and synthesised, and among them, several novel structures exhibited antiviral activity in the HCV replicon assay. Some of the new compounds were also found to inhibit HCV NS3 helicase function in?vitro, and one directly bound NS3 with a dissociation constant of 570?±?270?nM.
Unsymmetrical cyclotriazadisulfonamide (CADA) compounds as human CD4 receptor down-modulating agents
Demillo, Violeta G.,Goulinet-Mateo, Florian,Kim, Jessica,Schols, Dominique,Vermeire, Kurt,Bell, Thomas W.
supporting information; experimental part, p. 5712 - 5721 (2011/10/08)
Cyclotriazadisulfonamide (CADA) inhibits HIV at submicromolar levels by specifically down-modulating cell-surface and intracellular CD4. The specific biomolecular target of CADA compounds is unknown, but previous studies led to an unsymmetrical binding model. To test this model, methods were developed for effective synthesis of diverse, unsymmetrical CADA compounds. A total of 13 new, unsymmetrical target compounds were synthesized, as well as one symmetrical analogue. The new compounds display a wide range of potency for CD4 down-modulation in CHO-CD4-YFP cells. VGD020 (IC50 = 46 nM) is the most potent CADA compound discovered to date, and VGD029 (IC50 = 730 nM) is the most potent fluorescent analogue. Structure-activity relationships are analyzed from the standpoint of additive or nonadditive energy effects of different substituents. They appear to be consistent with the zipper-type mechanism in which entropy costs are reduced for additional stabilizing interactions between the small molecule and its protein target.
OXAZOLE AND THIAZOLE DERIVATIVES AND THEIR USES 2
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Page/Page column 46-47, (2008/12/08)
Compounds of formula (I): wherein A, X, R1, R2, R3, R4, R5, R6 and R8 are as defined in the Specification are useful in the treatment of diseases where enhanced M3 receptor activ
