《Discovery of N-ethylpyridine-2-carboxamide derivatives as a novel scaffold for orally active γ-secretase modulators》 was published in Bioorganic & Medicinal Chemistry in 2020. These research results belong to Sekioka, Ryuichi; Honda, Shugo; Honjo, Eriko; Suzuki, Takayuki; Akashiba, Hiroki; Mitani, Yasuyuki; Yamasaki, Shingo. Formula: C7H6BrNO2 The article mentions the following:
Gamma-secretase modulators (GSMs) are promising disease-modifying drugs for Alzheimer’s disease because they can selectively decrease pathogenic amyloid-β42 (Aβ42) levels. Here we report the discovery of orally active N-ethylpyridine-2-carboxamide derivatives as GSMs. The isoindolinone moiety of 5-[8-(benzyloxy)-2-methylimidazo[1,2-a]pyridin-3-yl]-2-ethyl-2,3-dihydro-1H-isoindol-1-one hydrogen chloride (1a) was replaced with a picolinamide moiety. Optimization of the benzyl group significantly improved GSM activity and mouse microsomal stability. 5-{8-[([1,1′-Biphenyl]-4-yl)methoxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-N-ethylpyridine-2-carboxamide hydrogen chloride (1v) potently reduced Aβ42 levels with an IC50 value of 0.091μM in cultured cells without inhibiting CYP3A4. Moreover, 1v demonstrated a sustained pharmacokinetic profile and significantly reduced brain Aβ42 levels in mice.Methyl 5-bromopicolinate(cas: 29682-15-3Formula: C7H6BrNO2) was used in this study.
Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. Pyridine is widely used in the precursor to agrochemicals and pharmaceuticals. Also, it is used as an important reagent and organic solvent.Formula: C7H6BrNO2