On October 3, 2019, Crew, Andrew P.; Wang, Jing; Berlin, Michael; Dragovich, Peter; Chen, Huifen; Staben, Leanna published a patent.Formula: C17H26O7S The title of the patent was Preparation of bifunctional PROTAC compounds and methods for degradation of targeted BRM proteins. And the patent contained the following:
The present disclosure relates to bifunctional compounds, e.g., I, their pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates, polymorphs and prodrugs which find utility as modulators of switch/sucrose non fermentable-related, matrix-associated, actin-dependent regulator of chromatin subfamily a member 2 (SMARCA2) or Brahma (BRM) (target protein), particularly to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The invention exhibits a broad range of pharmacol. activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein such as SMARCA4-related/deficient cancer, such as lung cancer or non-small cell lung cancer, are treated or prevented with compounds and compositions of the present disclosure. Thus, I was prepared by coupling of 2-[2-[2-[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]-1H-pyrazol-1-yl]ethoxy]eth oxy]acetic acid (preparation given) with (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-[4-(4-methylthiazol-5-yl )benzyl]pyrrolidine-2-carboxamide. A Western blot assay was used to assess the BRM degradation (Dmax and DC50) in SW 1573 cells; I displayed a DC50 ≥ 30 nM and DC50 > 75. The experimental process involved the reaction of tert-Butyl 2-(2-(2-(tosyloxy)ethoxy)ethoxy)acetate(cas: 882518-89-0).Formula: C17H26O7S
The Article related to chimeric mol preparation targeted brm smarca2 degradation ubiquitination, protac modulator preparation targeted ubiquitination brm degradation inhibition antitumor, von hippel lindau dipeptide ligand preparation brm protac inhibition and other aspects.Formula: C17H26O7S
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