Preparation of tritium‐labeled PF‐622, a novel fatty acid amide hydrolase inhibitor

Abstract

To make a detailed characterization of the mechanism of inhibition and selectivity of a novel fatty acid amide hydrolase inhibitor PF-622, 3 tritium isotopomers were prepared. [ H]PF-622a labeled at the piperazine ring B and [ H]PF-622b labeled at both the ring B and phenyl ring A were synthesized via catalytic H(hydrogen)-T(tritium) exchange, utilizing 1 equiv and excess of Crabtree's catalyst, respectively. The preparation of [ H]PF-622c labeled only at the phenyl ring A was achieved via tritiodebromination of the bromide precursor, using Pd(PPh ) as a catalyst. The observations from these tritiation reactions might open a new perspective in the labeling for the targets having a similar moiety.

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

“…In order to make a comprehensive characterization of the mechanism of inhibition and selectivity of PF-622, three tritium-labeled PF-622 analogues were prepared from PF-622 using the Ir-based Crabtree catalyst or simply Pd(PPh 3 ) 4 under tritium gas atmosphere (Scheme 158). 407 Bioanalytical tools that allow the identification of drug metabolites hold a great potential to discover new drugs and guide the selection of clinical candidates. In this aspect, isotopes of active drugs are commonly prepared to understand their metabolism and to identify and quantify specific metabolites.…”