1,3-Dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines as potent caspase-3 inhibitors.
Synthesis, biological evaluation and structure-activity relationships for a series of novel nonpeptide small molecule inhibitors of caspase-3 are described. Among the studied compounds, 8-sulfamide derivatives of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines have been identified as potent inhibitors of caspases-3. The most active compound within this series (8f) inhibited caspase-3 with IC(50)=4 nM.
Kravchenko
Dmitri V
DV
Department of Organic Chemistry, Chemical Diversity Research Institute, 114401 Khimki, Moscow Region, Russia.
Kysil
Vladimir V
VV
Ilyn
Alexey P
AP
Tkachenko
Sergey E
SE
Maliarchouk
Sergey
S
Okun
Ilya M
IM
Ivachtchenko
Alexandre V
AV
D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011804:Quinolines; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases