Discovery of N-ethylpyridine-2-carboxamide derivatives as a novel scaffold for orally active γ-secretase modulators was written by Sekioka, Ryuichi;Honda, Shugo;Honjo, Eriko;Suzuki, Takayuki;Akashiba, Hiroki;Mitani, Yasuyuki;Yamasaki, Shingo. And the article was included in Bioorganic & Medicinal Chemistry in 2020.Reference of 179232-29-2 This 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. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2Reference of 179232-29-2).
Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Reference of 179232-29-2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary