Structure-activity relationships for inhibitors of Pseudomonas aeruginosa exoenzyme S ADP-ribosyltransferase activity was written by Saleeb, Michael;Sundin, Charlotta;Aglar, Oeznur;Pinto, Ana Filipa;Ebrahimi, Mahsa;Forsberg, Aake;Schuler, Herwig;Elofsson, Mikael. And the article was included in European Journal of Medicinal Chemistry in 2018.Quality Control of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile This article mentions the following:
During infection, the Gram-neg. opportunistic pathogen Pseudomonas aeruginosa employs its type III secretion system to translocate the toxin exoenzyme S (ExoS) into the eukaryotic host cell cytoplasm. ExoS is an essential in vivo virulence factor that enables P. aeruginosa to avoid phagocytosis and eventually kill the host cell. ExoS elicits its pathogenicity mainly via ADP-ribosyltransferase (ADPRT) activity. The authors recently identified a new class of ExoS ADPRT inhibitors with in vitro IC50 of around 20 μM in an enzymic assay using a recombinant ExoS ADPRT domain. Herein, the authors report structure-activity relationships of this compound class by comparing a total of 51 compounds based on a thieno [2,3-d]pyrimidin-4(3H)-one and 4-oxo-3,4-dihydroquinazoline scaffolds. Improved inhibitors with in vitro IC50 values of 6 μM were identified. Importantly, the authors demonstrated that the most potent inhibitors block ADPRT activity of native full-length ExoS secreted by viable P. aeruginosa with an IC50 value of 1.3 μM in an enzymic assay. This compound class holds promise as starting point for development of novel antibacterial agents. In the experiment, the researchers used many compounds, for example, 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2Quality Control of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile).
2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile (cas: 70291-62-2) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. In conventional organic reductions, nitrile is reduced by treatment with lithium aluminium hydride to the amine. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis, which uses stannous chloride in acid.Quality Control of 2-Amino-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts