634908-68-2

Upstream product

• 156002-64-1 methyl 2-(tetrahydro-2H-pyran-4-yl)acetate 
• 138302-49-5 methyl 2-(dihydro-2H-pyran-4-(3H)-ylidene)acetate 
• 29943-42-8 Tetrahydro-4H-pyran-4-one 

Relevant academic research and scientific papers

Synthesis and activity of putative small-molecule inhibitors of the F-box protein SKP2

The tetrahydropyran 4-(((3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-4-phenylbutyl)amino)methyl)-N,N-dimethylaniline was reported to disrupt the SCFSKP2 E3 ligase complex. Efficient syntheses of this tetrahydropyran derivative and analogues, including the des-dimethyl derivative 4-(((3-(tetrahydro-2H-pyran-4-yl)-4-phenylbutyl)amino)methyl)-N,N-dimethylaniline, are described. The enantiomers of the des-dimethyl compound were obtained using Evans' chiral auxiliaries. Structure-activity relationships for these tetrahydropyrans and analogues have been determined by measurement of growth-inhibitory activities in HeLa cells, which indicated a non-specific mechanism of action that correlates with inhibitor lipophilicity. However, preliminary data with (R)-and (S)-4-(((3-(tetrahydro-2H-pyran-4-yl)-4-phenylbutyl)amino)methyl)-N,N-dimethylaniline showed enantioselective inhibition of the degradation of p27 in a cell-based assay that acts as a reporter of SKP2 activity.

COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER, COMPOSITIONS THEREOF AND METHODS THEREWITH

The present invention generally relates to compounds and compositions useful for the modulation of ligase activity. The invention further relates to Compounds of the Invention, compositions thereof, and methods for treating or preventing cancer, a neoplastic disorder, acute or chronic renal failure, an inflammatory disorder, an immune disorder, a cardiovascular disease, an effect of aging or an infectious disease comprising administering an effective amount of a Compound of the Invention. The invention further relates to the use of a Compound of the Invention as a preservative of a cell, blood, tissue or an organ or as an agent to modulate stem cells.