Synthesis and pharmacokinetic study of a 11C-labeled cholesterol 24-hydroxylase inhibitor using ‘in-loop’ [11C]CO2 fixation method

Autor:	Irina A. Pikuleva, Tuo Shao, Zhen Chen, Qingzhen Yu, Yihan Shao, Jiahui Chen, Xiaoyun Deng, Hualong Fu, Steven H. Liang, Jiyun Sun, Natalia Mast, Thomas Lee Collier, Lee Josephson, Jian Rong
Rok vydání:	2020
Předmět:	Programmed cell death Metabolite Clinical Biochemistry Pharmaceutical Science Neuroimaging Pharmacology 01 natural sciences Biochemistry Article Mice chemistry.chemical_compound Pharmacokinetics Drug Discovery medicine Cholesterol 24-Hydroxylase Animals Tissue Distribution Enzyme Inhibitors Cholesterol 24-hydroxylase Molecular Biology Carbon Isotopes medicine.diagnostic_test Molecular Structure 010405 organic chemistry Cholesterol Organic Chemistry Carbon fixation Carbon Dioxide Monooxygenase Aβ deposition Blockade 0104 chemical sciences Cytochrome P450 Family 010404 medicinal & biomolecular chemistry chemistry Positron emission tomography Positron-Emission Tomography Molecular Medicine Radiopharmaceuticals
Zdroj:	Bioorg Med Chem Lett
ISSN:	0960-894X
Popis:	Cholesterol 24-hydroxylase is a monooxygenase encoded by CYP46A1, which is specifically expressed in the brain where it controls cholesterol elimination by producing 24S-hydroxylcholesterol (24-HC) as the major metabolite. Selective blockade of CYP46A1 activity may suppress neuronal cell death, Aβ deposition and p-tau accumulation by decreasing 24-HC formation, which thereafter serves as potential therapeutic pathway for Alzheimer’s disease. In this work, we showcase the efficient synthesis and preliminary pharmacokinetic evaluation of a novel cholesterol 24-hydroxylase inhibitor 1 by positron emission tomography study.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5a7136fd1ed1ca9badb88b8f97228d6 https://doi.org/10.1016/j.bmcl.2020.127068 Zobrazit plný text záznamu Full Text from ScienceDirect