Yan, Luping published the artcileStructure-Activity Relationships for the Marine Natural Product Sintokamides: Androgen Receptor N-Terminus Antagonists of Interest for Treatment of Metastatic Castration-Resistant Prostate Cancer, Application of Methyl 4,4,4-trichlorobutanoate, the main research area is marine sintokamide androgen receptor antagonist prostate cancer antitumor preparation.
Synthetic analogs of the marine natural product sintokamides have been prepared in order to investigate the structure-activity relationships for the androgen receptor N-terminal domain (AR NTD) antagonist activity of the sintokamide scaffold. An in vitro LNCaP cell-based transcriptional activity assay with an androgen-driven luciferase (Luc) reporter was used to monitor the potency of analogs. The data have shown that the chlorine atoms on the leucine side chains are essential for potent activity. Analogs missing the nonchlorinated Me groups of the leucine side chains (C-1 and C-17) are just as active and in some cases more active than the natural products. Analogs with the natural R configuration at C-10 and the unnatural R configuration at C-4 are most potent. Replacing the natural propionamide N-terminus cap with the more sterically hindered pivaloylamide N-terminus cap leads to enhanced potency. The tetramic acid fragment and the Me ether on the tetramic acid fragment are essential for activity. The SAR optimized analog 76 is more selective, easier to synthesize, more potent, and presumed to be more resistant to proteolysis than the natural sintokamides.
Journal of Natural Products published new progress about Antitumor agents. 19376-57-9 belongs to class chlorides-buliding-blocks, name is Methyl 4,4,4-trichlorobutanoate, and the molecular formula is C5H7Cl3O2, Application of Methyl 4,4,4-trichlorobutanoate.
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Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics