title: 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.
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.
authors.affiliation: Department of Organic Chemistry, Chemical Diversity Research Institute, Khimki, Moscow Reg., Russia.
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Kravchenko
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Kuzovkova
authors.forename: Volodymyr M
authors.initials: VM
authors.lastname: Kysil
authors.forename: Sergey E
authors.initials: SE
authors.lastname: Tkachenko
authors.forename: Sergey
authors.initials: S
authors.lastname: Maliarchouk
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Okun
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Balakin
authors.forename: Alexandre V
authors.initials: AV
authors.lastname: Ivachtchenko
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D009025:Morpholines; D011758:Pyrroles; D011804:Quinolines; C505407:CASP3 protein, human; D053148:Caspase 3