Synthesis and structure-activity relationships of 5,6,7-substituted pyrazolopyrimidines: Discovery of a novel TSPO PET ligand for cancer imaging

Dewei Tang, Eliot T. McKinley, Matthew R. Hight, Md Imam Uddin, Joel M. Harp, Allie Fu, Michael L. Nickels, Jason R. Buck, H. Charles Manning

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Focused library synthesis and structure-activity relationship development of 5,6,7-substituted pyrazolopyrimidines led to the discovery of 2-(5,7-diethyl-2-(4-(2-fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N, N-diethylacetamide (6b), a novel translocator protein (TSPO) ligand exhibiting a 36-fold enhancement in affinity compared to another pyrazolopyrimidine-based TSPO ligand, 6a (DPA-714). Radiolabeling with fluorine-18 (18F) facilitated production of 2-(5,7-diethyl-2-(4-(2-[18F]fluoroethoxy) phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide (18F-6b) in high radiochemical yield and specific activity. In vivo studies of 18F-6b were performed which illuminated this agent as an improved probe for molecular imaging of TSPO-expressing cancers.

Original languageEnglish
Pages (from-to)3429-3433
Number of pages5
JournalJournal of Medicinal Chemistry
Volume56
Issue number8
DOIs
StatePublished - Apr 25 2013
Externally publishedYes

Fingerprint Dive into the research topics of 'Synthesis and structure-activity relationships of 5,6,7-substituted pyrazolopyrimidines: Discovery of a novel TSPO PET ligand for cancer imaging'. Together they form a unique fingerprint.

  • Cite this