Wang, Heng-Yen published the artcilePotent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker, Application In Synthesis of 844501-00-4, the publication is Journal of Medicinal Chemistry (2016), 59(10), 4913-4925, database is CAplus and MEDLINE.
Neuronal nitric oxide synthase (nNOS) is an important therapeutic target for the treatment of various neurodegenerative disorders. A major challenge in the design of nNOS inhibitors focuses on potency in humans and selectivity over other NOS isoforms. Here we report potent and selective human nNOS inhibitors based on the 2-aminopyridine scaffold with a central pyridine linker. Compound 14j, the most promising inhibitor in this study, exhibits excellent potency for rat nNOS (Ki = 16 nM) with 828-fold n/e and 118-fold n/i selectivity with a Ki value of 13 nM against human nNOS with 1761-fold human n/e selectivity. Compound 14j also displayed good metabolic stability in human liver microsomes, low plasma protein binding, and minimal binding to cytochromes P 450 (CYPs), although it had little to no Caco-2 permeability.
Journal of Medicinal Chemistry published new progress about 844501-00-4. 844501-00-4 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Amide,Boronic Acids,Boronic acid and ester, name is (1-(tert-Butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid, and the molecular formula is C8H15ClN2, Application In Synthesis of 844501-00-4.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem