Wu, Tianxiao published the artcileRational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold, Quality Control of 350-19-6, the publication is European Journal of Medicinal Chemistry (2022), 114096, database is CAplus and MEDLINE.
Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound I was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Addnl., compound I induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot anal. revealed that compound I inhibited the phosphorylation of TRK to block downstream pathways. Compound I also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, resp. Pharmacokinetic studies indicated that the oral bioavailability of compound I is 17.4%. These results demonstrate that compound I could serve as a novel lead compound for overcoming NTRK-fusion cancers.
European Journal of Medicinal Chemistry published new progress about 350-19-6. 350-19-6 belongs to esters-buliding-blocks, auxiliary class Fluoride,Benzene,Ester, name is Ethyl 3,5-difluorobenzoate, and the molecular formula is C19H14Cl2, Quality Control of 350-19-6.
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https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics