Application of 36620-11-8. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: Bis(norbornadiene)rhodium (I) tetrafluoroborate, is researched, Molecular C14H8BF4Rh, CAS is 36620-11-8, about The Discovery of Two Novel Classes of 5,5-Bicyclic Nucleoside-Derived PRMT5 Inhibitors for the Treatment of Cancer. Author is Quiroz, Ryan V.; Reutershan, Michael H.; Schneider, Sebastian E.; Sloman, David; Lacey, Brian M.; Swalm, Brooke M.; Yeung, Charles S.; Gibeau, Craig; Spellman, Daniel S.; Rankic, Danica A.; Chen, Dapeng; Witter, David; Linn, Doug; Munsell, Erik; Feng, Guo; Xu, Haiyan; Hughes, Jonathan M. E.; Lim, Jongwon; Sauri, Josep; Geddes, Kristin; Wan, Murray; Mansueto, My Sam; Follmer, Nicole E.; Fier, Patrick S.; Siliphaivanh, Phieng; Daublain, Pierre; Palte, Rachel L.; Hayes, Robert P.; Lee, Sandra; Kawamura, Shuhei; Silverman, Steven; Sanyal, Sulagna; Henderson, Timothy J.; Ye, Yingchun; Gao, Yuanwei; Nicholson, Benjamin; Machacek, Michelle R..
Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that catalyzes the post-translational sym. dimethylation of protein substrates. PRMT5 plays a critical role in regulating biol. processes including transcription, cell cycle progression, RNA splicing, and DNA repair. As such, dysregulation of PRMT5 activity is implicated in the development and progression of multiple cancers and is a target of growing clin. interest. Described herein are the structure-based drug designs, robust synthetic efforts, and lead optimization strategies toward the identification of two novel 5,5-fused bicyclic nucleoside-derived classes of potent and efficacious PRMT5 inhibitors. Utilization of compound docking and strain energy calculations inspired novel designs, and the development of flexible synthetic approaches enabled access to complex chemotypes with five contiguous stereo-centers. Addnl. efforts in balancing bioavailability, solubility, potency, and CYP3A4 inhibition led to the identification of diverse lead compounds with favorable profiles, promising in vivo activity, and low human dose projections.
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