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.

中文翻译：

---

使用“环内” [11C] CO2固定方法合成11C标记的胆固醇24-羟化酶抑制剂的合成和药代动力学研究。

胆固醇24-羟化酶，也称为CYP46A1（EC 1.14.13.98），是一种单加氧酶，是细胞色素P450家族的成员。CYP46A1在脑中特异性表达，它通过产生24S-羟基胆固醇（24-HC）作为主要代谢产物来控制胆固醇的消除。CYP46A1活性的调节可通过改变24-HC的形成来影响Aβ沉积和p-tau积累，此后可作为治疗阿尔茨海默氏病的潜在途径。在这项工作中，我们展示了用于正电子发射断层扫描的新型胆固醇24-羟化酶抑制剂1的有效合成和初步药代动力学评估。