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Vol. 30 No. 1 (2018): Vol 30 Issue 1

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A Novel 18F Labelled Imidazo-oxazolopyridine Derivative as b-Amyloid Imaging Agent: Synthesis and Preliminary Evaluation

https://doi.org/10.14233/ajchem.2018.20977
Shivani Singh
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. S.K. Mazumdar Road, Delhi-110 054, India; Department of Chemistry, University of Delhi, Delhi-110 007, India
Sweta Singh
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. S.K. Mazumdar Road, Delhi-110 054, India
Anjani Kumar Tiwari
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. S.K. Mazumdar Road, Delhi-110 054, India
Rakesh Kumar Sharma
Department of Chemistry, University of Delhi, Delhi-110 007, India
Rashi Mathur
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. S.K. Mazumdar Road, Delhi-110 054, India
Ankur Kaul
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organisation, Brig. S.K. Mazumdar Road, Delhi-110 054, India

Corresponding Author(s) : Sweta Singh

swetadcrs2017@gmail.com

Asian Journal of Chemistry, Vol. 30 No. 1 (2018): Vol 30 Issue 1

Abstract

Visualization of b-amyloid plaques in brain is pivotal for the diagnosis of Alzheimer’s disease. In the present study, we have designed, synthesized and evaluated an imidazo-oxazolopyridine derivative, 2-[2-(4-fluorophenyl)imidazo[1,2-a]pyridine-6-yl]oxazolo[4,5-b]pyridine (FPIPOP) as a promising candidate for imaging of Ab42 plaques using positron emission tomography (PET). Molecular docking of FPIPOP with Ab42 fibrils predicted good affinity. The target compound was synthesized with high chemical yield and easily reproducible steps. In assays using thioflavin S as a competitive ligand, FPIPOP showed good affinity towards Ab42 aggregates (Ki = 27.18 ± 4.7 nM). In PET experiments with normal Sprague dawley rat, high brain uptake and rapid clearance of activity was observed in cerebral cortex post i.v. injection (2.6 % ID/g for [18F]FPIPOP at 1 min and 0.8 % ID/g at 60 min). [18F]FPIPOP was found 76.4 % intact in brain for 60 min post injection. The ratio of radioactivity at maximal uptake to that at 60 min reached 20.5 for striatum, 26.4 for hippocampus and 33.1 for cerebellum. These results demonstrate that FPIPOP derivative has favourable in vivo brain pharmacokinetics and affinity for b-amyloid plaques; however, further optimization is required before pre-clinical evaluation of such skeletons in transgenic (Tg) mice models.

Keywords

Alzheimer’s disease b-Amyloid Imaging Positron emission tomography Imidazo-oxazolopyridine derivative
Singh, S., Singh, S., Tiwari, A. K., Sharma, R. K., Mathur, R., & Kaul, A. (2017). A Novel 18F Labelled Imidazo-oxazolopyridine Derivative as b-Amyloid Imaging Agent: Synthesis and Preliminary Evaluation. Asian Journal of Chemistry, 30(1), 183–190. https://doi.org/10.14233/ajchem.2018.20977
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