Microwave-assisted Organic Synthesis of a High-affinity Pyrazolo-pyrimidinyl TSPO Ligand

Overview

Journal Tetrahedron Lett

Publisher Elsevier

Specialty Chemistry

Date 2010 Aug 7

PMID 20689673

Citations 6

Authors

Dewei Tang

Jason R Buck

Matthew R Hight

H Charles Manning

Affiliations

Soon will be listed here.

Abstract

We herein report a dramatically improved total synthesis of the high-affinity translocator protein (TSPO) ligand DPA-714, featuring microwave-assisted organic synthesis (MAOS). Compared with previously described approaches, our novel MAOS method dramatically reduces overall reaction time without adversely effecting reaction yields. We envision that the described MAOS protocol may be suitably applied to high-throughput, diversity-oriented synthesis of novel compounds based on the pyrazolo-pyrimidinyl scaffold. Such an approach could accelerate the development of focused libraries of novel TSPO ligands with potential for future development as molecular imaging and therapeutic agents.

Citing Articles

Preclinical Evaluation of a Novel TSPO PET Ligand 2-(7-Butyl-2-(4-(2-[F]Fluoroethoxy)phenyl)-5-Methylpyrazolo[1,5-a]Pyrimidin-3-yl)-N,N-Diethylacetamide (F-VUIIS1018A) to Image Glioma.

Tang D, Li J, Nickels M, Huang G, Cohen A, Manning H Mol Imaging Biol. 2018; 21(1):113-121.

PMID: 29869061 PMC: 6953265. DOI: 10.1007/s11307-018-1198-7.

New structure-activity relationships of N-acetamide substituted pyrazolopyrimidines as pharmacological ligands of TSPO.

Li J, Schulte M, Nickels M, Manning H Bioorg Med Chem Lett. 2016; 26(15):3472-7.

PMID: 27353534 PMC: 4993599. DOI: 10.1016/j.bmcl.2016.06.041.

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

Tang D, McKinley E, Hight M, Uddin M, Harp J, Fu A J Med Chem. 2013; 56(8):3429-33.

PMID: 23521048 PMC: 3648642. DOI: 10.1021/jm4001874.

Rapid, Microwave-Assisted Organic Synthesis of Selective (V600E)BRAF Inhibitors for Preclinical Cancer Research.

Buck J, Saleh S, Uddin M, Manning H Tetrahedron Lett. 2012; 53(32):4161-4165.

PMID: 23180892 PMC: 3501741. DOI: 10.1016/j.tetlet.2012.05.137.

Quantitative preclinical imaging of TSPO expression in glioma using N,N-diethyl-2-(2-(4-(2-18F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide.

Tang D, Hight M, McKinley E, Fu A, Buck J, Smith R J Nucl Med. 2012; 53(2):287-94.

PMID: 22251555 PMC: 3391587. DOI: 10.2967/jnumed.111.095653.

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