Synthesis and structure-activity relationship of 4-substituted 2-(2-acetyloxyethyl)-8-(morpholine-4-sulfonyl)pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors

Dmitri V Kravchenko; Yulia A Kuzovkova; Volodymyr M Kysil; Sergey E Tkachenko; Sergey Maliarchouk; Ilya M Okun; Konstantin V Balakin; Alexandre V Ivachtchenko

doi:10.1021/jm048987t

Synthesis and structure-activity relationship of 4-substituted 2-(2-acetyloxyethyl)-8-(morpholine-4-sulfonyl)pyrrolo[3,4-c]quinoline-1,3-diones as potent caspase-3 inhibitors

J Med Chem. 2005 Jun 2;48(11):3680-3. doi: 10.1021/jm048987t.

Authors

Dmitri V Kravchenko¹, Yulia A Kuzovkova, Volodymyr M Kysil, Sergey E Tkachenko, Sergey Maliarchouk, Ilya M Okun, Konstantin V Balakin, Alexandre V Ivachtchenko

Affiliation

¹ Department of Organic Chemistry, Chemical Diversity Research Institute, Khimki, Moscow Reg., Russia.

PMID: 15916416
DOI: 10.1021/jm048987t

Abstract

Synthesis, biological evaluation, and SAR dependencies for a series of novel 1,3-dioxo-2,3-dihydro-1H-pyrrolo[3,4-c]quinoline inhibitors of caspase-3 are described. The inhibitory activity of the synthesized compounds is highly dependent on the nature of 4-substituents on the core scaffold. 4-methyl-and 4-phenyl-substituted derivatives, which were the most active compounds within this series, inhibited caspase-3 with IC50 of 23 and 27 nM, respectively.

MeSH terms

Apoptosis / drug effects
Caspase 3
Caspase Inhibitors*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
Jurkat Cells
Morpholines / chemical synthesis*
Morpholines / chemistry
Morpholines / pharmacology
Pyrroles / chemical synthesis*
Pyrroles / chemistry
Pyrroles / pharmacology
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology
Structure-Activity Relationship

Substances

Caspase Inhibitors
Enzyme Inhibitors
Morpholines
Pyrroles
Quinolines
CASP3 protein, human
Caspase 3