1H-pyrrolo[2,3-b]pyridine: A new scaffold for human neutrophil elastase (HNE) inhibitors was written by Crocetti, Letizia;Giovannoni, Maria Paola;Schepetkin, Igor A.;Quinn, Mark T.;Khlebnikov, Andrei I.;Cantini, Niccolo;Guerrini, Gabriella;Iacovone, Antonella;Teodori, Elisabetta;Vergelli, Claudia. And the article was included in Bioorganic & Medicinal Chemistry in 2018.Application of 1711-11-1 This article mentions the following:
Human neutrophil elastase (HNE) is a potent serine protease belonging to the chymotrypsin family. It is an important target for the development of novel and selective inhibitors for the treatment of inflammatory diseases, especially pulmonary pathologies. Here, we report the synthesis and biol. evaluation of a new series of HNE inhibitors with a pyrrolo[2,3-b]pyridine scaffold, which is an isomer of our previously reported indazoles, in order to assess how a shift of the nitrogen from position 2 to position 7 influences activity. The majority of new compounds were effective HNE inhibitors and had IC50 values in the micromolar/submicromolar range, with some compounds active in low nanomolar levels. For example, 2a and 2b inhibited HNE with IC50 values of 15 and 14 nM, resp. Mol. modeling of compounds differing in the position of heteroatom(s) in the bicyclic moiety and in the oxadiazole ring demonstrated that the calculated geometries of enzyme-inhibitor complexes were in agreement with the observed biol. activities. Docking experiments showed that orientation of the active pyrrolo[2,3-b]pyridines in the HNE catalytic triad Ser195-His57-Asp102 correlated with effectiveness of the inhibitor interaction with the enzyme. Thus, the pyrrolo[2,3-b]pyridine scaffold represents a novel scaffold for the development of potent HNE inhibitors. In the experiment, the researchers used many compounds, for example, 3-Cyanobenzoyl chloride (cas: 1711-11-1Application of 1711-11-1).
3-Cyanobenzoyl chloride (cas: 1711-11-1) belongs to organic chlorides. Organochlorines stimulate the central nervous system and cause convulsions, tremor, nausea, and mental confusion. Examples are dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, endosulfan, and dieldrin. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Application of 1711-11-1
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics