61667-16-1Relevant articles and documents
1,4,9-Triazaspiro[5.5]undecan-2-one Derivatives as Potent and Selective METTL3 Inhibitors
Dolbois, Aymeric,Bedi, Rajiv K.,Bochenkova, Elena,Müller, Anna,Moroz-Omori, Elena V.,Huang, Danzhi,Caflisch, Amedeo
, p. 12738 - 12760 (2021)
N6-methyladenosine (m6A) is the most frequent of the 160 RNA modifications reported so far. Accumulating evidence suggests that the METTL3/METTL14 protein complex, part of the m6A regulation machinery, is a key player in a variety of diseases including several types of cancer, type 2 diabetes, and viral infections. Here we report on a protein crystallography-based medicinal chemistry optimization of a METTL3 hit compound that has resulted in a 1400-fold potency improvement (IC50 of 5 nM for the lead compound 22 (UZH2) in a time-resolved F?rster resonance energy transfer (TR-FRET) assay). The series has favorable ADME properties as physicochemical characteristics were taken into account during hit optimization. UZH2 shows target engagement in cells and is able to reduce the m6A/A level of polyadenylated RNA in MOLM-13 (acute myeloid leukemia) and PC-3 (prostate cancer) cell lines.
PYRIMIDINE FGFR4 INHIBITORS
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Page/Page column 73, (2015/05/05)
Provided herein are compounds of Formula I useful as FGFR4 inhibitors, as well as methods of use of the same.
Effect of substituent structure on pyrimidine electrophilic substitution: A rebuttal
Jakubkiene, Virginija,?ikotiene, Inga
scheme or table, p. 2294 - 2298 (2012/04/10)
The report about a series of unexpected and obscure effects influencing the electrophilic nitrosation of activated pyrimidines (Tetrahedron 2007, 63, 5394) was shown to be erroneous. Instead of electrophilic substitution at position 5 of the pyrimidine ring, N-nitrosation of the secondary amino group in the 4-position of the pyrimidine ring took place. Moreover it was shown that the synthetic sequence for the preparation of purines is also incorrect.