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

Zhen Chen, Jiahui Chen, Natalia Mast, Jian Rong, Xiaoyun Deng, Tuo Shao, Hualong Fu, Qingzhen Yu, Jiyun Sun, Yihan Shao, Lee Josephson, Thomas Lee Collier, Irina Pikuleva, Steven H Liang

Bioorganic & medicinal chemistry letters 2020 May 01

filter terms:

Cholesterol 24-hydroxylase, also known as CYP46A1 (EC 1.14.13.98), is a monooxygenase and a member of the cytochrome P450 family. CYP46A1 is specifically expressed in the brain where it controls cholesterol elimination by producing 24S-hydroxylcholesterol (24-HC) as the major metabolite. Modulation of CYP46A1 activity may affect Aβ deposition and p-tau accumulation by changing 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 for use in positron emission tomography. Copyright © 2020 Elsevier Ltd. All rights reserved.

Citation

Zhen Chen, Jiahui Chen, Natalia Mast, Jian Rong, Xiaoyun Deng, Tuo Shao, Hualong Fu, Qingzhen Yu, Jiyun Sun, Yihan Shao, Lee Josephson, Thomas Lee Collier, Irina Pikuleva, Steven H Liang. Synthesis and pharmacokinetic study of a 11C-labeled cholesterol 24-hydroxylase inhibitor using 'in-loop' [11C]CO2 fixation method. Bioorganic & medicinal chemistry letters. 2020 May 01;30(9):127068