%0 Journal Article
%T Identification and Preclinical Evaluation of the Bicyclic Pyrimidine 污-Secretase Modulator BMS-932481
%J -
%D 2019
%R https://doi.org/10.1021/acsmedchemlett.8b00541
%X High Resolution Image Download MS PowerPoint Slide A triazine hit identified from a screen of the BMS compound collection was optimized for potency, in vivo activity, and off-target profile to produce the bicyclic pyrimidine 污-secretase modulator BMS-932481. The compound showed robust reductions of A汕1每42 and A汕1每40 in the plasma, brain, and cerebrospinal fluid of mice and rats. Consistent with the 污-secretase modulator mechanism, increases in A汕1每37 and A汕1每38 were observed, with no change in the total amount of A汕1每x produced. No Notch-based toxicity was observed, and the overall preclinical profile of BMS-932481 supported its further evaluation in human clinical trials
%U https://pubs.acs.org/doi/10.1021/acsmedchemlett.8b00541