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The present disclosure relates to [ 18 F]-labeled imidazopyridine derivatives or salts thereof as positron emission tomography (PET) radiotracers suitable for imaging the stress-signaling non-receptor tyrosine kinase c-abl, and their use in in vivo diagnosis, preclinical and clinical imaging, patient stratification on the basis of mutational status of c-abl and assessing response to therapeutic treatments. The present disclosure further relates to the use of [ 18 F]-labeled imidazopyridine derivatives as PET radiotracers. The disclosure also provides a process for the radiosynthesis of [ 18 F]-labeled imidazopyridinederivatives.
1 . A compound of Formula (I), or pharmaceutically acceptable salt thereof:
wherein
R 1 is —CH 2 CH 2 18 F or —OCH 2 CH 2 18 F when R 2 is —H, or
R 1 is —CH 2 CH 2 18 F or —OCH 2 CH 2 18 F when R 2 is —F.
2 . The compound of claim 1 , which is the compound of Formula (IIA) or a pharmaceutically acceptable salt thereof:
wherein R 2 is —H or —F.
3 . The compound of claim 1 , which is the compound of formula (IIB) or a pharmaceutically acceptable salt thereof:
wherein R 2 is —H or —F.
4 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of:
(1 S,2S)-2-fluoro-N-(6-(3-fluoro-2-(2-(fluoro- 18 F)ethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;
(1 S,2S)-2-fluoro-N-(6-(2-(2-(fluoro- 18 F)ethoxy)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;
(1 S,2S)-2-fluoro-N-(6-(2-(2-(fluoro- 18 F)ethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; and
(1 S,2S)-2-fluoro-N-(6-(3-fluoro-2-(2-(fluoro- 18 F)ethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide.
5 . A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
6 . A method for positron emission tomography (PET) imaging, the method comprising:
applying the compound of claim 1 to a biological sample as a PET tracer; and
imaging the compound using PET.
7 . The method of claim 6 , wherein the biological sample is from an AD (Alzheimer's disease)-induced mouse AD model or an alpha-synuclein PFF (pre-formed fibril)-induced mouse PD (Parkinson's disease) model.
8 . The method of claim 6 , wherein the biological sample is from a patient with a neurodegenerative disease.
9 . A method for positron emission tomography (PET) imaging, the method comprising:
administering the compound of claim 1 to a subject as a PET tracer, and imaging the compound using PET.
10 . The method of claim 9 , wherein the subject is an AD-induced mouse AD model or an alpha-synuclein PFF-induced mouse PD model.
11 . The method of claim 9 , wherein the subject is a patient with a neurodegenerative disease.