1444335-07-2

Basic information

• Product Name: 5-(benzyloxy)-3,4,6-trimethylpyridine-2-amine
• Synonyms: 5-(benzyloxy)-3,4,6-trimethylpyridine-2-amine
• CAS NO: 1444335-07-2
• Molecular Weight: 242.321
• Mol File: 1444335-07-2.mol

Chemical Properties

• CAS DataBase Reference: 5-(benzyloxy)-3,4,6-trimethylpyridine-2-amine(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(benzyloxy)-3,4,6-trimethylpyridine-2-amine(1444335-07-2)
• EPA Substance Registry System: 5-(benzyloxy)-3,4,6-trimethylpyridine-2-amine(1444335-07-2)

Safety Data

• Hazardous Substances Data: 1444335-07-2(Hazardous Substances Data)

Upstream product

• 58-56-0 pyridoxal hydrochloride 
• 102694-13-3 4,5-bis-chloromethyl-2-methyl-pyridin-3-ol 
• 100-44-7 benzyl chloride 
• 1616249-44-5 3-(benzyloxy)-2,4,5-trimethylpyridine 1-oxide 
• 1616249-43-4 3-(benzyloxy)-2,4,5-trimethylpyridine 
• 1444336-77-9 3-(benzyloxy)-6-bromo-2,4,5-trimethylpyridine 
• 1444336-68-8 6-bromo-2,4,5-trimethylpyridine-3-ol 
• 1444334-98-8 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]-1,1-diphenylmethanimine 
• 5622-78-6 2,4,5-trimethylpyridine-3-ol 
• 39984-50-4 4,5-bis(chloromethyl)-3-hydroxy-2-methylpyridinium chloride 

Downstream Products

• 1616249-64-9 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]thiophene-2-carboxamide 
• 1616249-63-8 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]-1-naphthamide 
• 1616249-62-7 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]benzo[d][1,3]dioxol-5-carboxamide 
• 1616249-61-6 N-(5-benzyloxy-3,4,6-trimethylpyridine-2-yl)-4-(tert-butyl)benzamide 
• 1616249-60-5 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]-4-methoxybenzamide 
• 1616249-59-2 N-(5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl)-4-fluorobenzamide 
• 1616249-58-1 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]benzamide 
• 1616249-55-8 N-(5-benzyloxy-3,4,6-trimethylpyridine-2-yl)cyclohexane carboxamide 
• 1616249-53-6 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]pivalamide 
• 1616249-52-5 N-[5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl]isobutyrylamide 

Relevant articles and documents

Novel pyridine bioisostere of cabozantinib as a potent c-met kinase inhibitor: Synthesis and anti-tumor activity against hepatocellular carcinoma

Two novel bioisosteres of cabozantinib, 3 and 4, were designed and synthesized. The ben-zene ring in the center of the cabozantinib structure was replaced by trimethylpyridine (3) and pyridine (4), respectively. Surprisingly, the two compounds showed extremely contrasting mesenchy-mal–epithelial transition factor (c-Met) inhibitory activities at 1 μM concentration (4% inhibition of 3 vs. 94% inhibition of 4). The IC50 value of compound 4 was 4.9 nM, similar to that of cabozantinib (5.4 nM). A ligand-based docking study suggested that 4 includes the preferred conformation for the binding to c-Met in the conformational ensemble, but 3 does not. The anti-proliferative activity of compound 4 against hepatocellular carcinoma (Hep3B and Huh7) and non-small-cell lung cancer (A549 and H1299) cell lines was better than that of cabozantinib, whereas 3 did not show a signifi-cant anti-proliferative activity. Moreover, the tumor selectivity of compound 4 toward hepatocellu-lar carcinoma cell lines was higher than that of cabozantinib. In the xenograft chick tumor model, compound 4 inhibited Hep3B tumor growth to a much greater extent than cabozantinib. The present study suggests that compound 4 may be a good therapeutic candidate against hepatocellular carci-noma.

Synthesis and activity of N-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)acetamide analogues as anticolitis agents via dual inhibition of TNF-α- and IL-6-induced cell adhesions

Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are the critical pro-inflammatory cytokines involved in the pathogenesis of inflammatory bowel disease (IBD). Inhibition of these cytokines and related signaling pathways has been a target for the development of IBD therapeutics. In the current study, 6-acetamido-2,4,5-trimethylpyridin-3-ol (1) and various analogues with the amido scaffold were synthesized and examined for their inhibitory activities in in vitro and in vivo IBD models. The parent compound 1 (1 μM) showed an inhibitory activity against TNF-α- and IL-6-induced adhesion of monocytes to colon epithelial cells, which was similar to tofacitinib (1 μM), a JAK inhibitor, but much better than mesalazine (1,000 μM). All the analogues showed a positive relationship (R2 = 0.8943 in a linear regression model) between the inhibitory activities against TNF-α-induced and those against IL-6-induced adhesion. Compound 2–19 turned out to be the best analogue and showed much better inhibitory activity against TNF-α- and IL-6-induced adhesion of the cells than tofacitinib. In addition, oral administration of compound 1 and 2–19 resulted in a significant suppression of clinical signs of TNBS-induced rat colitis, including weight loss, colon tissue edema, and myeloperoxidase activity, a marker for inflammatory cell infiltration in colon tissues. More importantly, compound 2–19 (1 mg/kg) was more efficacious in ameliorating colitis than compound 1 and sulfasalazine (300 mg/kg), the commonly prescribed oral IBD drug. Taken together, the results suggest that compound 2–19 can be a novel platform for dual-acting IBD drug discovery targeting both TNF-α and IL-6 signaling.

Synthesis, activity and mechanism of alkoxy-, carbamato-, sulfonamido-, thioureido-, and ureido-derivatives of 2,4,5-trimethylpyridin-3-ol against inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic immuno-inflammation in gastrointestinal tract. We have evaluated the activity of the compounds to inhibit the adhesion of monocytes to colon epithelial cells is triggered by a pro-inflammatory cytokine, tumour necrosis factor (TNF)-α. The in vitro activity of the compounds, 13b (an ureido-derivative), 14c, 14j, 14k, 14n (thioureido-), 18c and 18d (sulfonamido-), was in correlation with in vivo anti-colitis activity revealed as significant recovery in body- and colon-weights and colon myeloperoxidase level, a biochemical marker of inflammation reflecting neutrophil infiltration. In vivo, TNBS-induced changes in the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10, and TGF-β), NLRP3 inflammasome components (NLRP-3, Caspase-1, and IL-18), and epithelial junction molecules (E-cadherin, claudin2/3, and ZO-1) were blocked and recovered by oral administration of the compounds (1 mg/kg). Compound 14n which showed the best efficacy can be a promising lead for orally available therapeutics for pathology of IBD.

Inhibition of colitis by ring-modified analogues of 6-acetamido-2,4,5-trimethylpyridin-3-ol

6-Aminopyridin-3-ol scaffold has shown an excellent anti-inflammatory bowel disease activity. Various analogues with the scaffold were synthesized in pursuit of the diversity of side chains tethering on the C(6)-position. Structure-activity relationship among the analogues was investigated to understand the effects of the side chains and their linkers on their anti-inflammatory activities. In this study, structural modification moved beyond side chains on the C(6)-position and reached to pyridine ring itself. It expedited us to synthesize diverse ring-modified analogues of a representative pyridine-3-ol, 6-acetamido-2,4,5-trimethylpyridin-3-ol (9). In the evaluation of compounds on their inhibitory actions against TNF-α-induced adhesion of monocytic cells to colonic epithelial cells, an in vitro model mimicking colon inflammation, the effects of compounds 9, 17, and 19 were greater than tofacitinib, an orally available anti-colitis drug, and compound 17 showed the greatest activity. In addition, TNF-α-induced angiogenesis, which permits more inflammatory cell migration into inflamed tissues, was significantly blocked by compounds 17 and 19 in a concentration-dependent manner. In the comparison of in vivo therapeutic effects of compounds 9, 17, and 19 on dextran sulfate sodium (DSS)-induced colitis in mice, compound 17 was the most potent and efficacious, and compound 19 was better than compound 9 which showed a similar degree of inhibitory effect to tofacitinib. Taken together, it seems that either the trimethyl system or the hydroxyl group on the pyridinol ring is essential to the activity. This finding might become a new milestone in the development of pyridinol-based anti-inflammatory bowel disease agents.

Synthesis method of aminopyridine compounds

The invention provides a synthesis method of aminopyridine compounds. The synthesis method of the aminopyridine compounds comprises the following steps: under a heating condition, halogenated pyridineorganic matters and an ammoniation reagent are subjected to an ammoniation reaction to obtain an ammoniated product system, wherein in the ammoniation reaction, the temperature of the ammoniation reaction is 200-240 DEG C, and the ammoniation reagent is in a solid state and can be decomposed to generate ammonia gas; and the ammoniated product system is sequentially purified and salified to obtainthe aminopyridine compounds. The synthesis method does not need to add a solvent, so that the yield of three wastes can be greatly reduced; the type of the ammonification reagent and the ammonification reaction temperature are limited during the reaction process, such that the high reaction rate and the high conversion rate can be obtained without the addition of the catalyst, and the purification and salification process after the ammonification reaction is simple and has the good separation effect so as to substantially reduce the production cost and improve the product yield and the product purity. In addition, the synthesis method also has the advantages of good repeatability and the like.

PYRIDINOL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a pharmaceutical composition for preventing or treating inflammatory bowel disease, containing, as an active ingredient, a pyridinol derivative or a pharmaceutically acceptable salt thereof. A pyridinol derivative represented by chemical formula 1 or a pharmaceutically acceptable salt thereof has an excellent colitis inhibitory effect in an inflammatory bowel disease model, and thus can be useful as a medicine for preventing or treating inflammatory bowel disease.

Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells

Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17–28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 μM concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17–28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17–28 may be a lead compound to develop AMD therapeutics.

AMIDOPYRIDINOL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING SAME AS ACTIVE COMPONENT

The present invention relates to an amidopyridinol derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including an amidopyridinol derivative or a pharmaceutically acceptable salt thereof as an active component. An amidopyridinol derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof has an excellent antiangiogenic effect in a chorioallantoic membrane model, and thus is useful as an agent for preventing or treating diseases associated with angiogenesis, such as macular degeneration or arthritis, and also has an excellent colitis-inhibitory effect in a model of inflammatory bowel diseases, and thus is useful as an agent for preventing or treating inflammatory bowel diseases. Upon inoculation of lung cancer cells in a chorioallantoic membrane model, the amidopyridinol derivative of Chemical Formula 1 or the pharmaceutically acceptable salt thereof inhibits angiogenesis and tumor growth that are caused by tumorigenesis, and also inhibits the activity of cathepsin S that plays an important role in metastasis and invasion of cancer, and thus is useful as an inhibitor of cancer growth and metastasis.

Pharmaceutical composition for preventing or treating cancer comprising amidopyridinol derivative or a pharmaceutically acceptable salt

The present invention relates to an amidopyridinol derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including an amidopyridinol derivative or a pharmaceutically acceptable salt thereof as an active component. An amidopyridinol derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof has an excellent antiangiogenic effect in a chorioallantoic membrane model, and thus is useful as an agent for preventing or treating diseases associated with angiogenesis, such as macular degeneration or arthritis, and also has an excellent colitis-inhibitory effect in a model of inflammatory bowel diseases, and thus is useful as an agent for preventing or treating inflammatory bowel diseases. Upon inoculation of lung cancer cells in a chorioallantoic membrane model, the amidopyridinol derivative of Chemical Formula 1 or the pharmaceutically acceptable salt thereof inhibits angiogenesis and tumor growth that are caused by tumorigenesis, and also inhibits the activity of cathepsin S that plays an important role in metastasis and invasion of cancer, and thus is useful as an inhibitor of cancer growth and metastasis.

Synthesis and antiangiogenic activity of 6-amido-2,4,5-trimethylpyridin-3- ols

We recently reported that 6-aminoalkyl-2,4,5-trimethylpyridin-3-ols, novel series of 6-aminopyridin-3-ol-based antioxidants, have high antiangiogenic activities. In pursuit of wider variety in the analogues, we here report the synthesis and antiangiogenic activities of 6-amidoalkyl-2,4,5-trimethylpyridin- 3-ols, which would not be considered excellent antioxidants because of the poorer electron-donating effect of the C(6)-amido group than the corresponding C(6)-amino group. The selected 6-amido compounds showed up to several fold-higher antiangiogenic activities and up to an order of magnitude better antitumor activities in the chick embryo chorioallantoic membrane (CAM) assay than SU4312, a positive control. We also found that paracetamol, as a direct phenolic analogue of our simplest 6-amidopyridin-3-ol, showed a moderate level of antiangiogenic activity. We propose this study will offer a basis for a scaffold of novel angiogenesis inhibitors that can perturb angiogenesis-related pathologies.