biostudies-literatureGray BLHoward Hughes Medical InstituteNCI NIH HHS2621-4https://www.ebi.ac.uk/biostudies/studies/S-EPMC2652409biostudies-literatureUnknown10(13)Recognizing the value of including complex pyridines in small-molecule screening collections, we developed a previously unexplored [2 + 2 + 2]-cycloaddition of silyl-tethered diynes with nitriles. The tether provides high regioselectivity, while the solvent THF allows catalytic CpCo(CO)(2) to be used without exogenous irradiation. One of the resulting bicyclic and monocyclic (desilylated) pyridines was identified as an inhibitor of neuregulin-induced neurite outgrowth (EC(50) = 0.30 microM) in a screen that probes a pathway likely to be involved in breast cancers and schizophrenia.Organic lettersDiversity synthesis of complex pyridines yields a probe of a neurotrophic signaling pathway.PMC2652409P01 CA-078048P01 CA078048Schreiber SLGray BLKuai LWang XBrown WCfalseDiversity synthesis of complex pyridines yields a probe of a neurotrophic signaling pathway.Recognizing the value of including complex pyridines in small-molecule screening collections, we developed a previously unexplored [2 + 2 + 2]-cycloaddition of silyl-tethered diynes with nitriles. The tether provides high regioselectivity, while the solvent THF allows catalytic CpCo(CO)(2) to be used without exogenous irradiation. One of the resulting bicyclic and monocyclic (desilylated) pyridines was identified as an inhibitor of neuregulin-induced neurite outgrowth (EC(50) = 0.30 microM) in a screen that probes a pathway likely to be involved in breast cancers and schizophrenia.2008-01-01T00:00:00Z2008 Jul2025-04-20T02:09:14.804Z2019-03-27T00:21:06ZS-EPMC26524091851033310.1021/ol8004936