73590-93-9

Usage

Chemical Properties

Beige Color

Uses

Intermediate in the preparation of Omeprazole metabolites

Upstream product

• 202932-05-6 2-hydroxymethyl-3,5-dimethylpyridine 
• 695-98-7 2,3,5-trimethyl-pyridine 
• 70580-28-8 C₈H₁₁NO*ClH 
• 206990-64-9 acetic acid 3,5-dimethylpyridin-2-ylmethyl ester 
• 74409-42-0 2,3,5-trimethylpyridine 1-oxide 

Downstream Products

• 848695-25-0 BIIB₀₂₁ 

Relevant academic research and scientific papers

Synthesis and characterization of one impurity in esomeprazole, an antiulcerative drug

During drug synthesis, control of impurities is very important to get high-qualified drugs. A number of studies have devoted to synthesize the impurities and study the structures to support the method of purification. In this paper, we first synthesize one impurity in esomeprazole, rel-2-[[(3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-6-methoxy-1H-benzimidazole, with readily available raw materials, simple operation procedures and relatively mild reaction. Besides, we characterized its structure by MS, IR, 1H-NMR and HPLC analyses. The purity of target compound is as high as 99.58%, which can be used as the reference substance of the impurities of esomeprazole.

5-lipoxygenase-activating protein (FLAP) inhibitors. Part 4: Development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin- 2-ylmethoxy)-1 H -indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor

The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2- ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J. Med Chem.2009, 52, 5803-5815; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 213-217; Stock et al. Bioorg. Med. Chem. Lett.2010, 20, 4598-4601), SAR studies centering around the pyridine moiety led to the discovery of compounds that exhibit significantly increased potency in a human whole blood assay measuring LTB4 inhibition with longer drug preincubation times (15 min vs 5 h). Further studies identified 11cc with a potency of 2.9 nM in FLAP binding, an IC50 of 76 nM for inhibition of LTB4 in human blood (5 h incubation) and excellent preclinical toxicology and pharmacokinetics in rat and dog. 11cc also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. This compound has successfully completed phase 1 clinical studies in healthy volunteers and is currently undergoing phase 2 trials in asthmatic patients.

Synthesis and characterization of metabolites and potential impurities of the antiulcerative drug tenatoprazole

Tenatoprazole (Ulsacare) is a recently developed antiulcerative drug used for the treatment of both erosive and nonerosive gastroesophageal reflux disease. During the bulk synthesis of tenatoprazole, we have observed four impurities (tenatoprazole N-oxide, tenatoprazole sulfone N-oxide, N-methyl tenatoprazole, and desmethoxy tenatoprazole) and two metabolites (tenatoprazole sulfide and tenatoprazole sulfone). The present work describes the synthesis and characterization of these impurities. Copyright Taylor & Francis Group, LLC.

Structure-activity relationship of 2-[[(2-Pyridyl)methyl]thio]-1H- benzimidazoles as anti Helicobacter pylori agents in vitro and evaluation of their in vivo efficacy

A relationship between the structure of 21 2-[[(2-pyridyl)methyl]thio]- 1H-benzimidazoles (6) and their anti Helicobacter pylori activity expressed as minimum bactericidal concentration (MBC) values is described. Observed MBCs ranged from 256 to 1 μg/mL. The structure - activity relationship (SAR) showed that larger and more lipophilic compounds, especially compounds with such substituents in the 4-position of the pyridyl moiety, generally had lower MBC values. Four new compounds 'that were predicted to be potent by the established SAR model were synthesized and tested. One such compound, i.e., 2-[[(4-[(cyclopropylmethyl)oxy]3-methyl-2-pyridyl)methyl]thio]-1H- benzimidazole (18), was tested for in vivo efficacy in a mouse Helicobacter felis model (125 μmol/kg bid given orally for 4 days, n = 4). Unfortunately, antibacterial activity could not be clearly demonstrated in this model. Instead a potent acid secretion inhibition was observed. This finding was attributed to the methylthio compound being oxidized to the corresponding methyl sulfinyl derivative, i.e., a proton pump inhibitor, in vivo. Although the antibacterial activity had the potential of decreasing H. felis cell counts in vivo the proton pump inhibitory effect became dominant and actually promoted H. felis cell growth. Hence, we conclude that the antibacterial utility of the 2-[[(2-pyridyl)methyl]thio]1H-benzimidazoles (6) as a compound class is compromised by their propensity to become proton pump inhibitors upon metabolic oxidation in vivo.