Coutard, Bruno published the artcileAssessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery, Name: Thieno[2,3-b]pyrazin-7-amine, the publication is Antiviral Research (2014), 61-70, database is CAplus and MEDLINE.
Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based exptl. approach was applied to identify small mol. ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, resp. In a second stage, we set up a fragment-based X-ray crystallog. screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0 Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymic assays to assess their inhibition effect on the N7- and 2′-O-MTase enzymic activities: five of these fragment hits inhibit at least one of the two activities with IC50 ranging from 180 μM to 9 mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity mols. that bind to novel allosteric sites.
Antiviral Research published new progress about 59944-75-1. 59944-75-1 belongs to pyrazines, auxiliary class Other Aromatic Heterocyclic,Amine, name is Thieno[2,3-b]pyrazin-7-amine, and the molecular formula is C6H5N3S, Name: Thieno[2,3-b]pyrazin-7-amine.
Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem