1153686-88-4Relevant academic research and scientific papers
Discovery of sultam-containing small-molecule disruptors of the huntingtin–calmodulin protein–protein interaction
Aubé, Jeffrey,Frankowski, Kevin J.,Kapadia, Khushboo,Klus, Nicholas J.,McDonald, Peter,Muma, Nancy A.,Roy, Anuradha
, (2020)
The aberrant protein–protein interaction between calmodulin and mutant huntingtin protein in Huntington’s disease patients has been found to contribute to Huntington’s disease progression. A high-throughput screen for small molecules capable of disrupting this interaction revealed a sultam series as potent small-molecule disruptors. Diversification of the sultam scaffold afforded a set of 24 analogs or further evaluation. Several structure–activity trends within the analog set were found, most notably a negligible effect of absolute stereochemistry and a strong beneficial correlation with electron-withdrawing aromatic substituents. The most promising analogs were profiled for off-target effects at relevant kinases and, ultimately, one candidate molecule was evaluated for neuroprotection in a neuronal cell model of Huntington’s disease.
α-Haloarylsulfonamides: multiple cyclization pathways to skeletally diverse benzofused sultams
Rayabarapu, Dinesh Kumar,Zhou, Aihua,Jeon, Kyu Ok,Samarakoon, Thiwanka,Rolfe, Alan,Siddiqui, Hina,Hanson, Paul R.
experimental part, p. 3180 - 3188 (2009/08/15)
The development of new methods to skeletally diverse sultams based on a central α-halo benzene sulfonamide building block is reported. Several salient features of this building block are utilized in multiple reaction pathways, including the Heck reaction, C- and O-arylation, Sonogashira-Pauson-Khand, Sonogashira-intramolecular hydroamination, and domino aza-Michael-Heck for the generation of five-, six-, and seven-membered benzofused bicyclic and tricyclic sultams.
