Tanaka, Yuta; Seto, Masaki; Kakegawa, Keiko; Takami, Kazuaki; Kikuchi, Fumiaki; Yamamoto, Takeshi; Nakamura, Minoru; Daini, Masaki; Murakami, Masataka; Ohashi, Tomohiro; Kasahara, Takahito; Wang, Junsi; Ikeda, Zenichi; Wada, Yasufumi; Puenner, Florian; Fujii, Takahiro; Inazuka, Masakazu; Sato, Sho; Suzaki, Tomohiko; Oak, Jeong-Ho; Takai, Yuichi; Kohara, Hiroshi; Kimoto, Kouya; Oki, Hideyuki; Mikami, Satoshi; Sasaki, Minoru published the artcile< Discovery of Brain-Penetrant Glucosylceramide Synthase Inhibitors with a Novel Pharmacophore>, Product Details of C9H8Br2O2, the main research area is pyrrolopyridinone preparation glucosylceramide synthase inhibitor SAR.
Inhibition of glucosylceramide synthase (GCS) is a major therapeutic strategy for Gaucher’s disease and has been suggested as a potential target for treating Parkinson’s disease. Herein, authors report the discovery of novel brain-penetrant GCS inhibitors. Assessment of the structure-activity relationship revealed a unique pharmacophore in this series. The lipophilic ortho-substituent of aromatic ring A and the appropriate directionality of aromatic ring B were key for potency. Optimization of the absorption, distribution, metabolism, elimination, toxicity (ADMETox) profile resulted in the discovery of T-036, a potent GCS inhibitor in vivo. Pharmacophore-based scaffold hopping was performed to mitigate safety concerns associated with I. The ring opening of I resulted in another potent GCS inhibitor with a lower toxicol. risk, II, which reduced glucosylceramide in a dose-dependent manner in the plasma and cortex of mice. Finally, authors discuss the structural aspects of the compounds that impart a unique inhibition mode and lower the cardiovascular risk.
Journal of Medicinal Chemistry published new progress about Enzyme inhibitors (Glucosylceramide Synthase). 337536-14-8 belongs to class bromides-buliding-blocks, and the molecular formula is C9H8Br2O2, Product Details of C9H8Br2O2.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary