Pyrimidin-6-yl Trifluoroborate Salts as Versatile Templates for Heterocycle Synthesis
We report a novel and general method to access a highly under-studied privileged scaffold—pyrimidines bearing a trifluoroborate at C4, and highlight the broad utility of these intermediates in a rich array of downstream functionalization reactions. This chemistry is underpinned by the unique features of the trifluoroborate group; its robustness provides an opportunity to carry out chemoselective reactions at other positions on the pyrimidine while providing a pathway for elaboration at the C?B bond when suitably activated.
Cousins, David L.,Fricero, Prisca,Kopf, Kenji P. M.,McColl, Elliot J.,Czechtizky, Werngard,Lim, Yee Hwee,Harrity, Joseph P. A.
supporting information
p. 9412 - 9415
(2021/03/29)
Synthesis of 6-arylisocytosines and their potential for hydrogen bonding interactions
Abstract The synthesis of a number of 6-arylisocytosines, including linked bis-isocytosines, from the reaction of guanidine with β-ketoesters is described. The compounds were investigated for their ability to form hydrogen-bonded structural networks, and for their potential interactions with the telomeric quadruplex forming sequence AGGG(TTAGGG)3.
Patel, Alpa,Lewis, William,Searle, Mark S.,Stevens, Malcolm F.G.,Moody, Christopher J.
supporting information
p. 7339 - 7343
(2015/08/24)
HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase
The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing.