70258-18-3Relevant 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 (2021/09/13)
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.
Method for preparing chloromethylpyridine 2- chloride -5. (by machine translation)
-
Paragraph 0034; 0040-0186, (2019/12/29)
The mass percentage of, the precious metal in 2 - the precious metal catalyst of the noble metal 2 - catalyst of the " invention is that the mass percentage of 1%-10%; the noble 2 - metal 2 - in the precious metal; catalyst, 2 - containing the active, carbon or, aluminum oxide as the carrier is, the mass percent of the noble metal catalyst in the precious metal catalyst with the active carbon or alumina as the carrier 0.1%-0.5%; 2 - 2 - 82%, 98%, ". (by machine translation)
Green synthesis method of 2-chloro-5-chloromethylpyridine
-
Paragraph 0007; 0018-0023, (2019/12/02)
The invention discloses a green synthesis method of 2-chloro-5-chloromethylpyridine. The green synthesis method comprises the following steps: dissolving CCC (2-chloro-2-chloromethyl-2-cyanobutyl aldehyde) and DMF (N,N-dimethylformamide) in a solvent, introducing phosgene to carry out a cyclization reaction, after the reaction is finished, blowing off unreacted phosgene with nitrogen, desolventizing, and carrying out reduced pressure distillation to obtain a brown liquid that is the product 2-chloro-5-chloromethylpyridine. By utilizing the synthesis method disclosed by the invention, zero wastewater discharge can be realized, the production cost is reduced, the synthesis process is simple, and the product yield is high.