121495-79-2Relevant academic research and scientific papers
Discovery of Soticlestat, a Potent and Selective Inhibitor for Cholesterol 24-Hydroxylase (CH24H)
Koike, Tatsuki,Yoshikawa, Masato,Ando, Haruhi Kamisaki,Farnaby, William,Nishi, Toshiya,Watanabe, Etsurou,Yano, Jason,Miyamoto, Maki,Kondo, Shigeru,Ishii, Tsuyoshi,Kuroita, Takanobu
, p. 12228 - 12244 (2021/09/02)
Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (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, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative 1b. Optimization of 4-arylpyridine derivatives led us to identify 3v ((4-benzyl-4-hydroxypiperidin-1-yl)(2,4′-bipyridin-3-yl)methanone, IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, 3v resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound 3v (soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies.
Phase transfer-catalyzed, one-pot synthesis of some novel N-pyrimidinyl-N'-nicotinyl thiourea derivatives
Liu, Xing-Hai,Tan, Cheng-Xia,Weng, Jian-Quan
experimental part, p. 552 - 557 (2011/05/07)
A new series of acyl thiourea derivatives were synthesized in one-pot using PEG-600 as the phase transfer catalyst (PTC). The structures of title compounds were characterized by 1H NMR, IR, MS, and elemental analysis. In addition, the fungicidal activity of the acyl thiourea derivatives were tested, which showed that most of them exhibit moderate activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
Claisen condensation of N-methylpyrrolidinone and α-chloronicotinic esters
Kaminski, Thomas,Kirsch, Gilbert
, p. 229 - 234 (2008/09/19)
Reaction between α-halo-nicotinic esters and a nucleophilic source such as the N-methylpyrrolidin-2-one (NMP) gave unexpected results. The presence of the halide on the pyridine gave a very interesting migration reaction. Extension to 6-methylnicotinic ester derivatives lead to an unexpected carbanion condensation.
