Chemistry is traditionally divided into organic and inorganic chemistry. The former is the study of compounds containing at least one carbon-hydrogen bonds. 14433-76-2, Name is N,N-Dimethylcapramide, molecular formula is C12H25NO, belongs to amides-buliding-blocks compound, is a common compound. In a patnet, author is Kim, Gi-Dong, once mentioned the new application about 14433-76-2, Category: amides-buliding-blocks.
Design, synthesis and biological evaluation of N-(3-(1H-tetrazol-1-yl)phenyl)isonicotinamide derivatives as novel xanthine oxidase inhibitors
In our previous study, we reported a series of N-phenylisonicotinamide derivatives as novel xanthine oxidase (XO) inhibitors and identified N-(3-cyano-4-((2-cyanobenzyl)oxy)phenyl)isonicotinamide (compound 1) as the most potent one with an IC50 value of 0.312 mu M. To further optimize the structure and improve the potency, a structure-based drug design (SBDD) strategy was performed to construct the missing H-bond between the small molecule and the Asn768 residue of XO. We introduced a tetrazole moiety at the 3′-position of the phenyl to serve as an H-bond acceptor and obtained a series of N-(3-(1H-tetrazol-1-yl)phenyl)isonicotinamide derivatives (2a-t and 6-8). Besides, to investigate the influence of the amide-reversal, some N-(pyridin-4-yl)-3-(1H-tetrazol-1-yl)benzamide derivatives (3c, 3e, 3l, 3k and 3u) were also synthesized and evaluated. Biological evaluation and structure-activity relationship analysis demonstrated that the 3′-(1H-tetrazol-1-yl) moiety was an excellent fragment for the N-phenylisonicotinamide scaffold; a substituted benzyloxy, especially, an m-cyanobenzyloxy (e.g., 2s), linking at the 4′-position was welcome for the potency; and the amide-reversal could damage the potency, so maintenance of the N-phenylisonicotinamide scaffold was essential. In summary, starting from compound 1, the SBDD effort successfully identified a promising XO inhibitor 2s (IC50 = 0.031 mu M), with a 10-fold gain in potency. Its potency was very close to the positive control topiroxostat (IC50 = 0.021 mu M). A Lineweaver-Burk plot indicated that compound 2s acted as a mixed-type XO inhibitor. Molecular docking and molecular dynamics simulations revealed that the tetrazole moiety could occupy the Asn768-sub-pocket with N-4 atom accepting an H-bond from the Asn768 residue, as expected. (C) 2019 Elsevier Masson SAS. All rights reserved.
We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, 14433-76-2. The above is the message from the blog manager. Category: amides-buliding-blocks.