Koike, Tatsuki; Yoshikawa, Masato; Ando, Haruhi Kamisaki; Farnaby, William; Nishi, Toshiya; Watanabe, Etsurou; Yano, Jason; Miyamoto, Maki; Kondo, Shigeru; Ishii, Tsuyoshi; Kuroita, Takanobu published the artcile< Discovery of Soticlestat, a Potent and Selective Inhibitor for Cholesterol 24-Hydroxylase (CH24H)>, Computed Properties of 6942-39-8, the main research area is arylpyridine derivative soticlestat preparation drug design; cholesterol 24 hydroxylase inhibitor.
Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P 450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, authors report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative I. Optimization of 4-arylpyridine derivatives led authors to identify (4-benzyl-4-hydroxypiperidin-1-yl)(2,4′-bipyridin-3-yl)methanone (soticlestat, also known as TAK-935), (IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, soticlestat resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Soticlestat is currently under clin. investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies.
Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 6942-39-8 belongs to class bromides-buliding-blocks, and the molecular formula is C8H6BrFO2, Computed Properties of 6942-39-8.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary