N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors.
A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-L-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound.
Kiviranta
Päivi H
PH
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. paivi.kiviranta@uku.fi
Leppänen
Jukka
J
Rinne
Valtteri M
VM
Suuronen
Tiina
T
Kyrylenko
Olga
O
Kyrylenko
Sergiy
S
Kuusisto
Erkki
E
Tervo
Anu J
AJ
Järvinen
Tomi
T
Salminen
Antero
A
Poso
Antti
A
Wallén
Erik A A
EA
D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D008970:Molecular Weight; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors*; D014363:Tryptamines / Q000138:chemical synthesis* / Q000494:pharmacology*
D014363:Tryptamines; D009536:Niacinamide; C057564:tryptamide; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins