De novo synthesis and biological evaluation of C6″-substituted C4″-amide analogues of SL0101.
In an effort to improve upon the in vivo half-life of the known ribosomal s6 kinase (RSK) inhibitor SL0101, C4″-amide/C6″-alkyl substituted analogues of SL0101 were synthesized and evaluated in cell-based assays. The analogues were prepared using a de novo asymmetric synthetic approach, which featured Pd-π-allylic catalyzed glycosylation for the introduction of a C4″-azido group. Surprisingly replacement of the C4″-acetate with a C4″-amide resulted in analogues that were no longer specific for RSK in cell-based assays.
Departments of Pathology, Microbiology & Immunology and ⊥Cancer Biology, Vanderbilt University School of Medicine , Nashville, Tennessee 37232, United States.
Roman M
RM
Mrozowski
Zachary M
ZM
Sandusky
Rajender
R
Vemula
Bulan
B
Wu
Qi
Q
Zhang
Deborah A
DA
Lannigan
George A
GA
O'Doherty
D000577:Amides / Q000737:chemistry*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006031:Glycosylation; D006207:Half-Life; D015394:Molecular Structure; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000577:Amides; D001578:Benzopyrans; D009005:Monosaccharides; C497449:SL0101; D017346:Protein Serine-Threonine Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa