125189-20-0Relevant articles and documents
Identification of potent and selective MTH1 inhibitors
Petrocchi, Alessia,Leo, Elisabetta,Reyna, Naphtali J.,Hamilton, Matthew M.,Shi, Xi,Parker, Connor A.,Mseeh, Faika,Bardenhagen, Jennifer P.,Leonard, Paul,Cross, Jason B.,Huang, Sha,Jiang, Yongying,Cardozo, Mario,Draetta, Giulio,Marszalek, Joseph R.,Toniatti, Carlo,Jones, Philip,Lewis, Richard T.
, p. 1503 - 1507 (2016)
Structure based design of a novel class of aminopyrimidine MTH1 (MutT homolog 1) inhibitors is described. Optimization led to identification of IACS-4759 (compound 5), a sub-nanomolar inhibitor of MTH1 with excellent cell permeability and good metabolic stability in microsomes. This compound robustly inhibited MTH1 activity in cells and proved to be an excellent tool for interrogation of the utility of MTH1 inhibition in the context of oncology.
The Tautomeric Equilibria of Thio Analogues of Nucleic Acid Bases. Part 1. 2-Thiouracil: Background, Preparation of Model Compounds, and Gas-phase Proton Affinities
Katritzky, Alan R.,Baykut, Gokhan,Rachwal, Stanislaw,Szafran, Miroslaw,Caster, Kenneth C.,Eyler, John
, p. 1499 - 1506 (2007/10/02)
The preparation is reported of all four the monoalkyl derivatives of 2-thiouracil and four of the six possible dialkyl derivatives required as models for a study of the tautomeric equilibria by physical methods.Gas-phase proton affinities are determined using ion cyclotron resonance mass spectrometry, and are used to provide quantitative estimates of individual tautomer stabilities in the vapour state.These quantitative results agree well with qualitative deductions of predominant structures for the monoalkyl derivatives from i.r. spectroscopy.