Synthesis and biological evaluation of novel quinazoline-4-piperidinesulfamide derivatives as inhibitors of NPP1

The ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) was recently shown to promote mineralization of the aortic valve, hence, its inhibition represents a significant target. A quinazoline-4. piperidine sulfamide compound (QPS1) has been described as a specific and non-competitive inhibitor of NPP1. We report herein the synthesis and in vitro inhibition studies of novel quinazoline-4-piperidinc sulfamide analogues using QPS1 as the lead compound. Of the 26 derivatives prepared, four compound were found to have K-i < 105 nM against human NPP1. (C) 2018 Elsevier Masson SAS. All rights reserved