Title:Sodium-Proton Exchanger Isoform-1: Synthesis of a Potent Inhibitor Labeled with Deuterium and Carbon-14
VOLUME: 6 ISSUE: 1
Author(s):Bachir Latli, Nizar Haddad, Matt Hrapchak, Xudong Wei, Wenjun Tang, Jinhua J. Song and Chris H. Senanayake
Affiliation:Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, Ridgefield, Connecticut 06877 USA.
Keywords:NHE-1, Radiosynthesis, Carbon-14, deuterium, Comins reaction
Abstract:Sodium-proton exchangers, NHEs are plasma membrane proteins that are essential in the regulation of intracellular
pH of the myocardium. There are nine known variously expressed isoforms of NHEs with NHE-1 being the predominant
isoform in the heart. N-[4-(1-acetyl-piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (1) is a potent NHE
1inhibitor with good pharmacokinetics. It was prepared labeled with deuterium and carbon-14 to aid in drug metabolism,
pharmacokinetics, and other studies. The combination of Comins' reaction and reduction under deuterium gas was used to
access deuterium labeled (1) starting from deuterium labeled pyridine. Carbon-14 labeled zinc cyanide was used to prepare
[14C]-(1) in three steps, with a specific activity of 55.6 mCi/mmol.
