Highlights d KI-ARv-03 reduces AR protein levels and AR-driven transcription d KI-ARv-03 is deduced to be a potent, ultraselective inhibitor of CDK9 d Optimization led to the orally bioavailable and selective CDK9 inhibitor KB-0742 d KB-0742 displays potent anti-tumor activity in cancer models in vitro and in vivo

Carbon-11 (11C) is one of the most ideal positron emitters for labeling bioactive molecules for molecular imaging studies. The lack of convenient and fast incorporation methods to introduce 11C into organic molecules often hampers the use of this radioisotope. Here, a fluoride-mediated desilylation (FMDS) 11C-labeling approach is reported. This method relies on thermodynamically favored Si-F bond formation to generate a carbanion, therefore enabling the highly efficient and speedy incorporation of [11C]CO2 and [11C]CH3I into molecules with diversified structures. It provides facile and rapid access to 11C-labeled compounds with carbon-11 attached at various hybridized carbons as well as oxygen, sulfur and nitrogen atoms with broad functional group tolerance. The exemplified syntheses of several biologically and clinically important radiotracers illustrates the potentials of this methodology.

Reactions of K[RuNCl(HO)] with 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (dmbpy), and 4,4'-dimethoxy-2,2'-bipyridine (dmobpy) yielded the nitrido-bridged dinuclear complexes [RuN(L)Cl(DMF)] where L = bpy (1), dmbpy (2), and dmobpy (3). The crystal structures of these complexes reveal a linear Ru-N-Ru moiety with each ruthenium center bearing a bidentate diimine ligand. The complexes were further characterized by NMR, IR, and UV-vis spectroscopic methods and cyclic voltammetry. Because the compounds bear some structural similarities with the mitochondrial calcium uptake inhibitor Ru360, the ability of these complexes to act in this capacity was evaluated. The results demonstrate that 1-3 all fail to block mitochondrial calcium uptake, revealing new facets of the structure-activity relationships for ruthenium-based mitochondrial calcium uptake inhibitors.