Synthesis and evaluation of thiopyrano[3,4-c]quinoline-9-carboxamide derivatives as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)

Abstract

A series of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors, 5-oxo-2,4,5,6-tetrahydro-1H-thiopyrano[3,4-c]quinoline-9-carboxamide derivatives, were successfully synthesized and their PARP-1 inhibitory activity was evaluated. These compounds were prepared from carboxylic acid 7 and the appropriate amines, and a number of the synthesized compounds were found to have significant PARP-1 activity. Among them, 9m showed potent activity in a PARP-1 enzymatic assay and cell-based assay (IC 50 = 0.045 lM, ED 50 = 0.54 lM). Molecular modeling studies confirmed the obtained biological results.

Recent Advances in the Synthesis of Fused‐Cyclic Quinolines

“…1H-Thiopyrano [3,4-c]quinoline 224 exhibited potential inhibitory effects against PARP-1 (Scheme 73). [150] Exploring this bioactive scaffold could be facilitated through this approach.…”