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.

Fused pyridine derivatives R 0450 Synthesis and Chemical Transformations of 6-(Morpholine-4-sulfonyl)-quinoline-2,3,4-tricarboxylic Acid. -Key step in the synthesis of the pharmacologically interesting scaffold (VII), a potent inhibitor of caspase-3, is the Pfitzinger reaction of indole (I) with succinate (II). -(KRAVCHENKO, D. V.; KYSIL, V. M.; ILYN, A. P.; TKACHENKO, S. E.; MALIARCHOUK, S.; OKUN, I. M.; IVACHTCHENKO*, A. V.; Synth. Commun. 36 (2006) 7-9, 911-917; ChemDiv. Inc., San Diego, CA 92121, USA; Eng.) -M. Bohle 35-152

No abstract

We present a convenient synthesis of novel heteroaryl-fused 3-oxo-1,4-thiazepine-5-carboxamides and 5-oxo-1,4-thiazepine-3-carboxamides using a modification of four-component Ugi condensation. We demonstrate the usefulness and versatility of the developed approach for the synthesis of variously substituted compounds and discuss the scope and limitations of the chemistry involved.