Oxadiazole-carbonylaminothioureas as SIRT1 and SIRT2 inhibitors.
A new inhibitor for human sirtuin type proteins 1 and 2 (SIRT1 and SIRT2) was discovered through virtual database screening in search of new scaffolds. A series of compounds was synthesized based on the hit compound (3-[[3-(4-tert-butylphenyl)1,2,4-oxadiazole-5-carbonyl]amino]-1-[3-(trifluoromethyl)phenyl]thiourea). The most potent compound in the series was nearly as potent as the reference compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide).
Huhtiniemi
Tero
T
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. tero.huhtiniemi@uku.fi
Suuronen
Tiina
T
Rinne
Valtteri M
VM
Wittekindt
Carsten
C
Lahtela-Kakkonen
Maija
M
Jarho
Elina
E
Wallén
Erik A A
EA
Salminen
Antero
A
Poso
Antti
A
Leppänen
Jukka
J
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D012663:Semicarbazides; C005151:thiosemicarbazide; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2; D037761:Sirtuins