Yu, Lei published the artcileA structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFRL858R/T790M mutant with improved pharmacokinetic properties, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, the publication is European Journal of Medicinal Chemistry (2017), 1107-1117, database is CAplus and MEDLINE.
Structural optimization of pyrido[2,3-d]pyrimidin-7-ones was conducted to yield a series of new selective EGFRT790M inhibitors with improved pharmacokinetic properties. One of the most promising compound 9s (N-(3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)-5-(trifluoromethyl)phenyl)acrylamide) potently suppressed EGFRL858R/T790M kinase and inhibited the proliferation of H1975 cells with IC50 values of 2.0 nM and 40 nM, resp. The compound dose-dependently induced reduction of the phosphorylation of EGFR and downstream activation of ERK in NCI-H1975 cells. It also exhibited moderate plasma exposure after oral administration and an oral bioavailability value of 16%. Compound 9s may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer (NSCLC) patients.
European Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C15H14O, Recommanded Product: 6-(4-Methylpiperazin-1-yl)pyridin-3-amine.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics