TITLE:
Nω-Nitro-Nω’-Substituted Guanidines: A Simple Class of Nitric Oxide Synthase Inhibitors
AUTHORS:
Christophe D. Guillon, David D. Wisnoski, Jaya Saxena, Ned D. Heindel, Diane E. Heck, Donald J. Wolff, Jeffrey D. Laskin
KEYWORDS:
Nitro-Guanidines, Nitric Oxide Synthase (NOS), Isoforms, Selective Inhibitors
JOURNAL NAME:
Modern Research in Inflammation,
Vol.3 No.2,
May
6,
2014
ABSTRACT: A series of Nω-nitro-Nω’-substituted
guanidines has been prepared as potential inhibitors of the human Nitric Oxide
Synthase (NOS) isoforms. The reported utility of amino-guanidine and nitroarginine
in iNOS inhibition points to a potential similar utility for analogs of
nitro-guanidine. The compound library was tested against the three isoforms of
Nitric Oxide Synthase (eNOS, iNOS and nNOS). Several candidates showed
excellent activity and good selectivity for nNOS. One particular compound even
demonstrated good selectivity for iNOS. The potential usefulness of such
selective inhibitors is discussed.