1444335-16-3

Upstream product

• 58-56-0 pyridoxal hydrochloride 
• 100-44-7 benzyl chloride 
• 111-26-2 hexan-1-amine 
• 1444336-77-9 3-(benzyloxy)-6-bromo-2,4,5-trimethylpyridine 
• 1444336-68-8 6-bromo-2,4,5-trimethylpyridine-3-ol 
• 5622-78-6 2,4,5-trimethylpyridine-3-ol 
• 39984-50-4 4,5-bis(chloromethyl)-3-hydroxy-2-methylpyridinium chloride 

Relevant academic research and scientific papers

In vitro and in vivo inhibitory activity of 6-amino-2,4,5-trimethylpyridin-3-ols against inflammatory bowel disease

Although the pathogenesis of inflammatory bowel disease (IBD) is complex, attachment and infiltration of leukocytes to gut epithelium induced by pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) represents the initial step of inflammation in IBD. Previously, we have reported that some 6-amino-2,4,5-trimethylpyridin-3-ols have significant levels of antiangiogenic activity via PI3K inhibition. Based on the reports that angiogenesis is involved in the aggravation of IBD and that PI3K is a potential target for IBD therapy, we investigated whether the scaffold has inhibitory activity against in vitro and in vivo models of colitis. Many analogues showed >80% inhibition against TNF-α-induced monocyte adhesion to colon epithelial cells at 1?μM. Compound 8m showed IC50?=?0.19?μM, which is about five orders of magnitude better than that of 5-aminosalicylic acid (5-ASA, IC50?=?18.1?mM), a positive control. In a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis, orally administered 8m dramatically ameliorated TNBS-induced colon inflammation. It was demonstrated by a high level of suppression in myeloperoxidase (MPO), a surrogate marker of colitis, as well as almost perfect recovery of colon and body weights in a dose-dependent manner. Compared to sulfasalazine, a prodrug of 5-ASA, compound 8m showed >300-fold better efficacy in those parameters. Taken together, 6-amino-2,4,5-trimethylpyridin-3-ols can provide a novel platform for anti-IBD drug discovery.

6-Amino-2,4,5-trimethylpyridin-3-ols: A new general synthetic route and antiangiogenic activity

A new synthetic strategy for preparation of a wide range of 6-amino-2,4,5-trimethylpyridin-3-ols from pyridoxine·HCl via a six-step sequence has been developed. This approach features an introduction of various amino groups to C(6)-position of 3-benzyloxy-6-bromo-2,4,5-trimethylpyridine (13), a key intermediate, by a Buchwald-Hartwig amination reaction using palladium(0) transition metal, which certainly renders an expanded scope of amino substituents. Some analogs prepared using the methods described here showed high level of antiangiogenic and antitumor activities in chick chorioallantoic membrane (CAM) assay, demonstrating the potential of these new aminopyridinols as antiangiogenic agents.

6-AMINOPYRIDINE-3-OL DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENTS FOR PREVENTING OR TREATING DISEASES CAUSED BY ANGIOGENESIS

Provided are 6-aminopyridin-3-ol derivatives or pharmaceutically acceptable salts thereof and pharmaceutical compositions for the prevention or treatment of disease caused by angiogenesis containing disease caused by angiogenesis including the same as an active ingredient. The 6-aminopyridin-3-ol derivatives represented by Formula 1 or the pharmaceutically acceptable salts thereof have excellent neoangiogenesis inhibition effects in the chorioallantoic membrane model, and accordingly, they are suitable for use as a drug for the prevention or treatment of disease caused by angiogenesis.