892276-50-5Relevant academic research and scientific papers
Scaffolding-Induced Property Modulation of Chemical Space
D?mling, Alexander,Di Lorenzo, Vincenzo,Kalinowska-T?u?cik, Justyna,Kurpiewska, Katarzyna,Li, Jingyao,Patil, Pravin,Ruiz-Moreno, Angel J.,Velasco-Velázquez, Marco A.
, p. 356 - 360 (2020)
Physicochemical property switching of chemical space is of great importance for optimization of compounds, for example, for biological activity. Cyclization is a key method to control 3D and other properties. A two-step approach, which involves a multicomponent reaction followed by cyclization, is reported to achieve the transition from basic moieties to charge neutral cyclic derivatives. A series of multisubstituted oxazolidinones, oxazinanones, and oxazepanones as well as their thio and sulfur derivatives are synthesized from readily available building blocks with mild conditions and high yields. Like a few other methods, MCR and cyclization allow for the collective transformation of a large chemical space into a related one with different properties.
Structure-activity relationships in human toll-like receptor 8-active 2,3-diamino-furo[2,3- c ]pyridines
Salunke, Deepak B.,Yoo, Euna,Shukla, Nikunj M.,Balakrishna, Rajalakshmi,Malladi, Subbalakshmi S.,Serafin, Katelyn J.,Day, Victor W.,Wang, Xinkun,David, Sunil A.
, p. 8137 - 8151 (2012/11/07)
In our ongoing search toward identifying novel and synthetically simpler candidate vaccine adjuvants, we hypothesized that the imidazo[1,2-a]pyrazines, readily accessible via the Groebke-Blackburn-Bienaymé multicomponent reaction, would possess sufficient structural similarity with TLR7/8-agonistic imidazoquinolines. With pyridoxal as the aldehyde component, furo[2,3-c]pyridines, rather than the expected imidazo[1,2-a]pyridines, were obtained, which were characterized by NMR spectroscopy and crystallography. Several analogues were found to activate TLR8-dependent NF-κB signaling. In a focused library of furo[2,3-c]pyridines, a distinct SAR was observed with varying substituents at C2. In human PBMCs, none of the furo[2,3-c]pyridines showed any proinflammatory cytokine induction but upregulated several chemokine ligand genes. In immunization studies in rabbits, the most active compound showed prominent adjuvantic effects. The complete lack of proinflammatory cytokine induction coupled with strong adjuvantic activity of the novel furo[2,3-c]pyridines render this hitherto unknown chemotype an attractive class of compounds which are expected to be devoid of local or systemic reactogenicity.
