In 2022,Ikeda, Shuhei; Kajita, Yuichi; Miyamoto, Maki; Matsumiya, Kouta; Ishii, Tsuyoshi; Nishi, Toshiya; Gay, Sean C.; Lane, Weston; Constantinescu, Cristian C.; Alagille, David; Papin, Caroline; Tamagnan, Gilles; Kuroita, Takanobu; Koike, Tatsuki published an article in European Journal of Medicinal Chemistry. The title of the article was 《Design and synthesis of aryl-piperidine derivatives as potent and selective PET tracers for cholesterol 24-hydroxylase (CH24H)》.Recommanded Product: 18621-18-6 The author mentioned the following in the article:
Cholesterol 24-hydroxylase (CH24H, CYP46A1) is a cytochrome P 450 family enzyme that maintains the homeostasis of brain cholesterol. Soticlestat, a potent and selective CH24H inhibitor, is in development as a therapeutic agent for Dravet syndrome and Lennox-Gastaut syndrome. Herein, we report the discovery of aryl-piperidine derivatives as potent and selective CH24H positron emission tomog. (PET) tracers which can be used for dose guidance of a clin. CH24H inhibitor and as a diagnostic tool for CH24H-related pathol. Starting from compound I (IC50 = 16 nM, logD = 1.7), which was reported as a CH24H inhibitor with lower lipophilicity, a 18F-labeling site (3-fluoroazetidine) was incorporated by structure-based drug design (SBDD) utilizing the co-crystal structure of a compound I analog. Subsequent optimization to adjust key parameters for PET tracers, such as potency, lipophilicity, brain penetration, and unbound plasma protein binding, enabled compound II [Ar = 4-FC6H4, X = N] (IC50 = 8.8 nM) and compound II [Ar = 4-chloropyrazol-1-yl, X = CH] (IC50 = 8.7 nM) as PET imaging candidates. Selectivity of these compounds for CH24H was validated by a brain distribution study using CH24H-WT and KO mice. In non-human primate PET imaging, [18F] labeled analogs showed similar regional uptake in the brain, indicating that these tracers were specific to the CH24H-expressed regions and validated the expression of CH24H in the living brain by different tracers. After reading the article, we found that the author used Azetidin-3-ol hydrochloride(cas: 18621-18-6Recommanded Product: 18621-18-6)
Azetidin-3-ol hydrochloride(cas:18621-18-6) is one of azetidine.Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products.Recommanded Product: 18621-18-6 Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor.
Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts