Back to Search Start Over

Synthesis and preliminary evaluation of 18F-labeled 1-(6,7-dimethyl-4-(methylamino)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-2-(trans-2-(6-fluoropyridin-3-yl)cyclopropyl)ethan-1-one for imaging muscarinic acetylcholine receptor subtype 4

Synthesis and preliminary evaluation of 18F-labeled 1-(6,7-dimethyl-4-(methylamino)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-2-(trans-2-(6-fluoropyridin-3-yl)cyclopropyl)ethan-1-one for imaging muscarinic acetylcholine receptor subtype 4

Authors :
Tuo Shao
Qingzhen Yu
Yiding Zhang
Gangqiang Wang
Steven H. Liang
Ming-Rong Zhang
Lee Josephson
Shaofa Sun
Kuan Hu
Katsushi Kumata
Wakana Mori
Masayuki Fujinaga
Xiaoyun Deng
Jian Rong
Akiko Hatori
Yihan Shao
Source :
Tetrahedron Letters. 61:152060
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

Abstract

Positive allosteric modulators of muscarinic acetylcholine receptor subtype 4 have been identified as promising activators for the treatment of neurological disorders and neurodegenerative diseases, including schizophrenia, Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Herein we report the synthesis and preliminary evaluation of a 18F-labeled positron emission tomography ligand based on a M4 activator (7). 18F-Isotopologue of 7 was prepared in a reasonable radiochemical yield with high radiochemical purity (>99%) and high molar activity (>37 GBq/µmol). In vitro autoradiography studies indicated that the ligand possessed moderate in vitro specific binding. Dynamic PET studies in vivo demonstrated that [18F]7 (also named as [18F]M4R-1911) failed to cross the blood–brain barrier. Therefore, further chemical scaffold optimization in chemotype of 7 is necessary to overcome limited brain permeability and improve specific binding.

Details

ISSN :
00404039
Volume :
61
Database :
OpenAIRE
Journal :
Tetrahedron Letters
Accession number :
edsair.doi...........37d36b19f58ce4579e959f51c06bccb3
Full Text :
https://doi.org/10.1016/j.tetlet.2020.152060