Evolution of the Thienopyridine Class of Inhibitors of I魏B Kinase-尾: Part I: Hit-to-Lead Strategies was written by Morwick, Tina;Berry, Angela;Brickwood, Janice;Cardozo, Mario;Catron, Katrina;DeTuri, Molly;Emeigh, Jonathan;Homon, Carol;Hrapchak, Matt;Jacober, Stephen;Jakes, Scott;Kaplita, Paul;Kelly, Terence A.;Ksiazek, John;Liuzzi, Michel;Magolda, Ronald;Mao, Can;Marshall, Daniel;McNeil, Daniel;Prokopowicz, Anthony III;Sarko, Christopher;Scouten, Erika;Sledziona, Cynthia;Sun, Sanxing;Watrous, Jane;Wu, Jiang Ping;Cywin, Charles L.. And the article was included in Journal of Medicinal Chemistry in 2006.Synthetic Route of C10H9ClN2O2 This article mentions the following:
High-throughput screening is routinely employed as a method for the identification of novel hit structures. Large numbers of active compounds are typically procured in this way and must undergo a rigorous validation process. This process is described in detail for a collection of screening hits identified as inhibitors of I魏B kinase-尾 (IKK尾), a key regulatory enzyme in the nuclear factor-魏B (NF-魏B) pathway. From these studies, a promising hit series was selected. Subsequent lead generation activities included the development of a pharmacophore hypothesis and structure-activity relationship (SAR) for the hit series. This led to the exploration of related scaffolds offering addnl. opportunities, and the various structural classes were comparatively evaluated for enzyme inhibition, selectivity, and drug-like properties. A novel lead series of thienopyridines was thereby established, and this series advanced into lead optimization for further development. In the experiment, the researchers used many compounds, for example, Ethyl-2-chloro-3-cyano-6-methylisonicotinate (cas: 40108-12-1Synthetic Route of C10H9ClN2O2).
Ethyl-2-chloro-3-cyano-6-methylisonicotinate (cas: 40108-12-1) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Synthetic Route of C10H9ClN2O2
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics