107512-35-6

The invention belongs to the technical field of medicine, and particularly relates to a preparation method of a pantoprazole intermediate 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride. The preparation method comprises the following steps: using 3-hydroxyl-2-methyl-4-pyrone as a starting raw material, and then only performing five-step reaction to obtain the pantoprazole intermediate 2-chloromethyl-3,4-dimethoxy pyridine hydrochloride. The preparation method reduces the reaction steps, shortens the reaction cycle, improves the working efficiency, and increases the yield coefficient.

Helicobacter pylori urease belongs to a family of highly conserved urea- hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K+-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K+- ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pK(a)-value of the pyridine, the pK(a)-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of β- mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 μmol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 μmol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

A new total synthesis in five steps of alkaloid Orelline is reported.The methodology involves metalation of methoxypyridines to afford 2-halo-3,4-dimethoxypyridine on which an homocoupling reaction is performed to build the 2,2'-bipyridyl structure of the

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The compound of the formula STR1 wherein R1 is hydrogen, fluorine, methoxy or trifluoromethyl, R2 is a C1-8 alkyl, R3 is a C1-8 alkyl which may be fluorinated, and n is 0 or 1, or a pharmacologically acceptable salt thereof is useful for prevention and treatment of digestive ulcers (e.g. gastric ulcer, duodenal ulcer) and gastritis.